Whitechapel - Exotic Virology 2013-05-24T22:37:42-07:00 http://freakangels.com/whitechapel/ Lussumo Vanilla & Feed Publisher Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252073#Comment_252073 2010-07-27T10:45:16-07:00 2010-07-27T10:45:49-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 After gracious clearance from Mr. Ellis, here we are with a thread to discuss the biology of exotic viruses and what interesting technologies there are out there involving viruses. I can field ...
I can field questions, of course, but I don't really want this to become Lecture Time starring John Skylar. Not the place for it. In a way I'm hoping that the creative consciousness of Whitechapel is going to spur me to new ways of thinking about the work that I do.

Anyway, to launch the thread, I want to share a couple of resources that are good for quickly familiarizing yourself with some of the cool things in virology.

The first is virology blog, by Dr. Vincent Racaniello. Dr. Racaniello also has a podcast called THIS WEEK IN VIROLOGY, which comes highly recommended. It's also really accessible, so you can jump right in no matter what you know.

There is also a totally open journal called Public Library of Science (PLoS), started by the decorated Dr. Harold Varmus. No paywalls here! PLoS has a subjournal called PLoS Pathogens, and their "Pearls" column includes short, entry-level introductions to various topics. They are collected here.

Oh, and I almost forgot to mention INTERFERON FORCE, a comic put out by a company that makes reagents for studying the immune system. It's a fun, kinda cheesy summary of innate immunity, which is important against viruses. It would be nice if it credited any of its authors or artists more prominently, but it's a reagent supply company, I don't think they know from comics.

Anyhow, that's a bunch of reading and I'm sure others will have things they want to share. I have to get back to working on this virus that makes monkeys foam blood out of their noses (Nipah virus as portrayed in a recent paper, link with photos if you're curious)]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252080#Comment_252080 2010-07-27T11:17:10-07:00 2013-05-24T22:37:42-07:00 oddbill http://freakangels.com/whitechapel/account.php?u=4272 Can you talk a little about the use of viruses as a delivery mechanism for engineered genetic material into living cells? Is there a state of the art that isn't well reported? Are there any ...
Is there a state of the art that isn't well reported? Are there any therapies in human patients yet that use this technique?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252118#Comment_252118 2010-07-27T21:16:06-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 Ah, the ol' gene therapy question. Virus-vectored genetic engineering is great in experimental applications. We use it all the time to make genetically engineered cell lines or mice. So far in ...
So far in humans, though? Has a nasty habit of causing cancer. The new viral genes stick themselves into something useful a lot of the time. A couple of kids died in 2005, after a trial of that sort of thing, and it's kind of hampered the field.

But I think herpes viruses, if we ever come to understand them better, might end up as a viable method of gene therapy, because their genomes don't integrate. It's a pet theory though. Dunno if anybody agrees.

One thing that I think is under-reported is oncolytics. Aka, using viruses to kill cancer. The immune system usually alerts the body to an infected cell using the inflammatory Type I Interferon (IFN) system, which usually causes the immune system to kill infected cells. Turns out, cancer is inflammatory too, so the cancers that survive are often ones with mutations in the IFN system. So, viruses that are stopped by IFN and don't make you sick, are often very good at killing cancer cells. There's a couple of human trials with this, one of them using a thing called reovirus, by a group in Canada. There's also a group in New York using a bird virus called Newcastle Disease Virus for certain oncolytic applications. So yeah...virus infections to cure cancer. Kind of blows my mind.

Anybody know of a thing I forgot?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252129#Comment_252129 2010-07-28T00:38:07-07:00 2013-05-24T22:37:42-07:00 Nygaard http://freakangels.com/whitechapel/account.php?u=431 Curious about the potential for spectacle in viral gene therapy - curing cancer is of course way more spectacular than cosmetic applications, but a viral infection that, say, changes your skin ... Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252130#Comment_252130 2010-07-28T01:02:45-07:00 2013-05-24T22:37:42-07:00 smileyfish http://freakangels.com/whitechapel/account.php?u=8832 Cool stuff! Gotta say that Nipah virus does not look like fun at all. A friend of mine recently completed a PhD looking at applications of network theory in epidemiology. Turns out networks can ...
A friend of mine recently completed a PhD looking at applications of network theory in epidemiology. Turns out networks can help to predict virus spread in a population, and can also identify the number of immune individuals required in a population to provide "herd immunity" (i.e. enough individuals are immune that the virus dies out in that population). Text is here for those interested. Useful for humans and livestock, but not so good for viruses in wild animal populations.

I'm an aquatic ecologist, so don't do any virology work myself, but do find it fascinating. I'm also keen on the potential for gene therapy, as it currently looks like the only possible way to solve a few of my own medical problems. Shame about the tumours!]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252169#Comment_252169 2010-07-28T08:08:41-07:00 2010-07-28T08:11:40-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 @nygaard Well, currently, with the risks of viral vectored gene therapy, it's not worth it to have cosmetic applications, as any gene therapy could potentially cost you your life. However, let's ...
However, let's say we got past that obstacle. We will eventually, I suspect. Changing the colour of your skin or adding feathers are two very different things that illustrate the limitations of this technology. I'm sure a lot of you remember Alpha Centauri, the computer game from the 90s. There was one tech that had this quote:

"Remember, genes are NOT blueprints. This means you can't, for example, insert 'the genes for an elephant's trunk' into a giraffe and get a giraffe with a trunk. There are no genes for trunks. What you CAN do with genes is chemistry, since DNA codes for chemicals. For instance, we can in theory splice the native plants' talent for nitrogen fixation into a terran plant."

Macro-structures take a complex program of genes to make, so feathers would be pretty hard to do. Most viruses are a pretty small package, and so inserting multiple genes is really tricky. Bigger viruses have their own issues with gene therapy. So feathers, or other things like them, would not be easy.

Skin pigments? Easy, just one gene. I expect that'll be one of the first things that gets made once the technology is robust and safe.

@smileyfish Yeah, Nipah's no fun at all.

Combining network theory and epidemiology is something that's been on my mind for a long time. Someday I'd like to see epidemiologists using simulators not just to respond to existing pathogens, but to predict when and where new pathogens are going to emerge, so that we can defend ourselves proactively. Your friend's work sounds awesome.

How do you feel about J. Craig Venter's explorations of genomes in the sea? I thought the number of viruses they pulled out was outright staggering.

EDIT: Actually, come to think of it, the first outbreak of Nipah virus occurred on a farm and went from bats to pigs to humans. Your friend's network theory applications could really help in predicting and preventing the spread of future Nipah outbreaks, given their tendency to happen on farms.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252250#Comment_252250 2010-07-28T19:16:02-07:00 2013-05-24T22:37:42-07:00 Zeebo http://freakangels.com/whitechapel/account.php?u=1651 Hope you don't mind if an immunologist jumps into the mix. I'd just like to mention another powerful technology paradigm that's growing thanks to viral genetic engineering: induced pluripotent ...
I'd just like to mention another powerful technology paradigm that's growing thanks to viral genetic engineering: induced pluripotent cells (iPS). We're still not sure if they're true stem cells or not, but I think this method could prove more useful for many of the organismal changes when people think of "genetic engineering."

For a quick primer, genetic engineering obviously edits genes, which internally control the behavior of the cell. Another less-talked about option is developmental engineering. If you have some stem cells, it's theoretically easier to grow them in specified environments that encourage the development of particular cell types. This environment often mimics the localized environment of an organ developing in a fetus.

So, another option for people who hope to some day have horns and demonic hemipenises, developmental engineering coupled with modern medicine's amazing surgical capabilities might be an easier approach than viral engineering. Granted, surgery and in vitro growth have their own pitfalls, but it's an idea.

Anyway, back to this idea of iPS. It's been all the rage in the news because it's a potential for unlimited sources of patient-specific stem cells. How do you make stem cells from fully developed cells? You insert the DNA for 3 or 4 developmental genes into them. Once you "kick start" this developmental program, the cell's innate machinery takes over and maintains a stem-cell-like state. Viruses are great at inserting DNA, but you have the problem of cancer, as detailed earlier. There are a lot of ways of getting around this now. One way is to create a self-excising virus, which pairs perfectly with the fact that cells can maintain the stem cell state once they've been converted. Another option is non-integrating viruses that create their products, but aren't inserted into the genome. There are more exotic ways of doing things too, like mechanically punching holes into cells and letting DNA diffuse into them.

As for Venter, he does a lot of crazy and interesting stuff, but I think much of his acclaim comes from being a very good salesman. His oceanic sequencing project is a great idea and pulled out a lot of interesting data, but, unfortunately, it has very little metadata associated with it. Lots of conclusions can still be reached from raw, loosely-ordered data sets, but they're harder to link to previously-discovered information. Then again, that's kind of a hand-wavey argument.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252273#Comment_252273 2010-07-28T22:09:01-07:00 2013-05-24T22:37:42-07:00 kozmund http://freakangels.com/whitechapel/account.php?u=547 I think, if anything, viral vectors are closer to cosmetic use than clinical use. You'll have to forgive me for the next sentence which is annotated in parenthesis for clarification. When you're ...
That is to say, applying a gene vector viruses to the epidermis isn't so risky as to put it out of the equation for the body mod crowd, if there was the available expertise and gear. Applying a vector where they'd be fairly permanent is a different matter. I'm still waiting to see the first EGFP temporary tattoo.

(P.S. Not to be insensitive, but I would personally take leukemia over SCID any day of the week.)
(P.P.S. Nothing in this post should be understood as medical advice. Always consult your physician before using a viral vector to modify the DNA in any of your cells.)]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252331#Comment_252331 2010-07-29T09:00:40-07:00 2010-07-29T11:43:31-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 @Zeebo Ooh! An immunologist! Good to see ya. I'm tempted to joke about how I expect you'll provide a strong response in 5-9 days, but maybe that's too much. Yeah, iPS is a great technology. ...
Ooh! An immunologist! Good to see ya. I'm tempted to joke about how I expect you'll provide a strong response in 5-9 days, but maybe that's too much.

Yeah, iPS is a great technology. Of course, I think that viral gene "therapy" will be useful in the context of iPS cells too, to edit the cells in culture before they're differentiated and returned to the patient. Still, there's the problem with any stem cells that they can fail to differentiate in-patient and cause cancer too. The tech needs to be worked out.

I tend to agree with you on Venter's showmanship. I got my undergrad from a lot of people who worked with Leroy Hood, and they were no big fans of Venter, so I'm a little biased. Calling the human genome his IP...I mean really....

@kozmund

The DNA changes that are caused in gene therapy are heritable to the cells' progeny, so your theory doesn't really fly. Actually I'd say the *least* dangerous application is in cell types that divide slowly or don't divide at all, because then if the cell goes haywire it might die via apoptosis before bad things happen. Bone marrow divides slowly, and the SCID trial patients only got leukemia a couple years after treatment. If it had been skin cells, I imagine they would have gotten the cancer to manifest a lot faster.

I think, actually, that there are techniques involving electroporation of injected DNA that the body mod crowd might want to see. But the viral vectors? I'd say it's more dangerous, not less, than other applications.

(Electroporation: a technique where you use electrical current to force DNA into cells, making them express whatever the DNA codes for. The results last for a few days before they clear up. It's being used for vaccine development right now.)

And while I would also take leukemia over SCID if offered the choice, I'd take SCID over *incurable* leukemia.


On an unrelated note, I think smileyfish asked me a question about lyssaviruses in another thread. I mean, aside from Rabies being basically the zombie virus (makes you go crazy, mindless, and bite people), I don't really study them. They're similar in replication to Nipah, though. But there are some key points of difference, specifically that the genomes are smaller and they tend to form visible replication complexes.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252395#Comment_252395 2010-07-29T17:06:05-07:00 2013-05-24T22:37:42-07:00 Brazen http://freakangels.com/whitechapel/account.php?u=4750 Howdy, Biochemist/Cell Physiologist here. I've noticed the bulk of this conversation has been about retroviruses (viruses that incorporate their DNA into a host's genome). What about Adenoviruses? ...
I've noticed the bulk of this conversation has been about retroviruses (viruses that incorporate their DNA into a host's genome). What about Adenoviruses? These are viruses that drop a genomic payload (which modern science can program) into a host. This payload does not incorporate into the host genome and is therefore transient. That said, infection is silly efficient across most cell types and you wouldn't have to worry about cancer risks. Think about it, you could temporarily pump yourself full of some gene... say flourescent GFP for a couple weeks.

Relating to Adenoviruses there is a movement in biotech to engineer a viable hybrid adeno-lentivirus which would have the high infection potential of an adenovirus, as well as the ability to stably incoporate DNA into a hosts genome like a retrovirus. It would be the best of both worlds (sans the cancer risk).

Also, since this thread seems to have a genetic engineering slant, the curious should check out cre-lox technology. This stuff represents the bleeding edge of transgenic animal engineering. Essentially you add DNA sequences (lox sites) to a gene of interest that are recognized by a recombinase (cre). Cre recombinase then chops out the DNA inbetween these two sites. This allows site directed deletions of DNA (losses of function), or with some extra engineering, site directed activation of genes. Cre recombinase can be coupled to specific gene promotors which can limit recombination events to specific cell types, or specific developmental stages giving spatial control of events. There are also inducible cre recombinase derivatives that only "turn on" (get transported into the nuclease) with the addition of chemicals (or other stimulation) giving spatial control of recombination too. This is what I'm currently doing to study gene function in multicellular animals... so much mouse breeding.

The thing that always blows me away about cre lox is that with available human embryonic stem cells, one can grow humans with suicide switches built into their genome. They recieve the right chemical dead. They fail to recieve treatment with a chemical dead. This is something that could ACTUALLY be done. Scary eh?

Another neat genetic engineering tool in its embryonic stage is modular engineered proteins. The only example I know of is are the zinc finger nucleases which can be programmed to cleave DNA at any specific DNA sequence. Here is a movie by the people who make them. While only useful for knockouts right now, I think that this kind of thing could be thing that makes gene therapy actually possible.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252397#Comment_252397 2010-07-29T17:07:55-07:00 2013-05-24T22:37:42-07:00 Brazen http://freakangels.com/whitechapel/account.php?u=4750 Crumbs! Forgot to mention that there are targetted adenovriuses out there now that selectively infect the a specific organ... like the kidneys or pancreas. Which is pretty useful. Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252398#Comment_252398 2010-07-29T17:36:23-07:00 2010-07-30T15:36:13-07:00 Finagle http://freakangels.com/whitechapel/account.php?u=5254 Personally, I'm leery of touching any of this flavor of biotech until the intellectual property rights get thrashed out. You've still got farmers getting sued for infringement from patented seeds ...
(ETA: I'm a former instructor in biomedical ethics and do take this seriously) .]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252416#Comment_252416 2010-07-29T22:12:14-07:00 2013-05-24T22:37:42-07:00 graelignites http://freakangels.com/whitechapel/account.php?u=5086 So you're saying I'm going to need some oncolytics to cure the cancer I get from my genetically engineered demonic hemipenises? Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252501#Comment_252501 2010-07-30T12:56:54-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 The first part is directed to Brazen. They recieve the right chemical dead. They fail to recieve treatment with a chemical dead. I believe we already have humans like this. Strangely, all of ...
They recieve the right chemical dead. They fail to recieve treatment with a chemical dead.


I believe we already have humans like this. Strangely, all of them tend to die when you give them the chemical "cyanide" and live unless deprived of the chemical "water." It seems like it would be too time intensive and useless to engineer people who were keyed to dying on condition of something else, unless you're making Replicants. But it's not really virology, so I'll move on.

So, when it comes to Adenoviruses, I think you might have a misconception of how gene therapy is supposed to work. For gene therapeutics to persist, you have to achieve integration of the viral genome into the host. Otherwise, the viral genome degrades and you lose the correction and after enough transient treatments you're immune to all the adenovirus serotypes. Host integrases, or engineered integrases, can make adenoviruses a good vector for gene therapy, but unless you integrate, it's not a good therapy. But with integration, you get all the problems of retroviral gene therapy. So, no, that's not a safer alternative.

Protein engineering is pretty fascinating, though! I'm especially excited about groups making proteins with atypical amino acids.

Anyway, moving away from that response, a great paper turned up today about Ebola virus and Marburg virus sequences that have integrated into host genomes. This is really amazing, because they are RNA viruses and strictly speaking that should never happen. Even more interestingly, the proteins that are found in the host genomes are truncated versions that contain only the parts of the Ebola/Marburg proteins that SHUT DOWN IMMUNITY. And these sequences have apparently wandered around with their hosts for 48 million years. I'm puzzled and amazed.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=252689#Comment_252689 2010-07-31T16:52:29-07:00 2010-07-31T16:52:57-07:00 Brazen http://freakangels.com/whitechapel/account.php?u=4750 @ John Skylar: Fair enough on the suicide switch. Also, I'm aware that Adenoviruses are poor candidates for gene therapy. I was just saying they have a number of cool genetic engineering ...
Fair enough on the suicide switch. Also, I'm aware that Adenoviruses are poor candidates for gene therapy. I was just saying they have a number of cool genetic engineering applications is all.

I did misspeak about the organ specific Adenoviruses though. I meant to say that they are Adeno-associated Viruses (AAV). These are apparently the gene therapy golden standard now. The lab nextdoor to mine uses a specific AAV to selectively infect pancreatic islets for gene therapy applications. AAV's are highly efficient at infection, can infect dormant or dividing cells, and certain types of AAVs are tissue specific (pancreas and brain for instance). Not only this but they do not cause any pathogenic symptoms in mammals infected with the virus. MOST IMPORTANTLY they are able to stably integrate their genetic payloads in a SPECIFIC genetic site (AAVS1) with no known side effects and extremely low off site integration. How cool is that?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=253096#Comment_253096 2010-08-02T21:18:30-07:00 2013-05-24T22:37:42-07:00 Zeebo http://freakangels.com/whitechapel/account.php?u=1651 RE Adenoviruses: I think adenoviruses could also be very useful in the future once we've done more systems biological mapping of human development. Then you could use adenoviruses to "kick ... I think adenoviruses could also be very useful in the future once we've done more systems biological mapping of human development. Then you could use adenoviruses to "kick start" a certain cellular program, much the same as iPS technology does now.

Fun fact: stem cells are often very good at silencing retroviruses (IE stem cells can eliminate or strongly decrease the expression of retroviruses in their genome). This is one of the key reasons iPS cells work without a bunch of strange growth aberrations. The retrovirus is incorporated into an adult cell, it causes the cell to become a stem cell, and then the stem cell "program" silences the retrovirus while using its own machinery to maintain the stem cell state.

@Brazen
AAVs are awesome, but I wouldn't call them the ubervirus. As far as I know, their genetic payload is relatively small, which limits their usefulness. Though they don't cause much active immune response, they do seem to elicit a strong neutralizing antibody response, which would probably decrease their whole-animal infection capacity significantly.

As far as cre-lox, I wouldn't really call it bleeding edge any more. It's a fairly old technology in mice and human cells do fairly well using the mouse proteins it requires. (That portage was actually part of my thesis project). Even more interesting is the games people have started to play with cre-lox and flp-frt. Both do essentially the same thing, as described above, but they do it different ways. This lets you do things like build logic gates. Here's a simplified diagram (the area between two similar sites is cut out):

lox---Coolstuff1---frt---Coolstuff2---lox---frt---Coolstuff3---frt
If the cell is exposed to Cre first (it eliminates the region between lox sites), then Coolstuff1 and Coolstuff2 are eliminated and Coolstuff3 becomes permanent. If the cell receives Flp first, then some cells will lose Coolstuff3, some will lose Coolstuff2, and some will lose both. But, in cells that lose Coolstuff2, Coolstuff1 becomes permanent, whereas those that only lose Coolstuff3, Coolstuff1 and 2 can still be eliminated by Cre. I know it's a little confusing, but it lets you build some really gnarly If-Then statements and such.

But, this is all kind of getting away from the exotic virology subject and delving more into genetic engineering. As far as viruses go, how about mimi/mamaviruses, the largest ever discovered. As far as I know, they have many similarities with bacteria as far as complexity of function and size are concerned. I'm not sure about the current evolutionary thinking though. I know they were once touted as the "missing link" between viruses and bacteria, but I'm not sure if that's still a possibility. I've always thought that viruses developed from bacteria rather than the other way around since viruses all need a host to replicate and it's far more likely they had a host during evolution than all of them discarding their self-sustaining traits.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=253279#Comment_253279 2010-08-03T20:05:17-07:00 2010-08-04T11:34:26-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I'm down with AAV, but like Zeebo said, the capacity is rather limited. You know what would be cool? If we could figure out why AAV's integration site is where it is, and force that into some ...
At least it's not a paramyxovirus like Nipah. If it was, the genome size would always have to be divisible by six. Weird stuff.

Viral origins, though, now that's exotic. I've heard the idea of mimiviruses being a primordial virus, but I'm not sure I buy into it. TWiV, which I linked to up top, has covered mimis, mamas, and pseudomimis in the past, and kind of flirted with the theory that a virus that huge could be a viral progenitor.

Now, that's one theory. Other theories suggest that viruses arose sort-of on their own, or that they were an accident. That might be legit, too.

I have a slightly different theory, though. It's not supported by data, it's not mainstream. Don't take it as expertise. It's just speculation.

But what if viruses are an ancient means of cell-cell communication that went horribly wrong? What if they're responsible for a lot of the diversity that we see today, and maybe even still generate diversity, but we don't know about it because we've only paid attention to the viruses that make us sick?

There might be millions of human viruses that don't cause any symptoms. There might be some that save your life. I just don't know.

So maybe, just maybe, cells traded genetic information via viruses at some point in the past. Or maybe they still do. And perhaps a couple of defective viruses made this into a process that can make people sick.

I'd like to know what other people think about that idea.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=253283#Comment_253283 2010-08-03T20:31:44-07:00 2013-05-24T22:37:42-07:00 Fishelle http://freakangels.com/whitechapel/account.php?u=8854 @John Skylar I don't know much of anything about virology, or science in general for that matter, so I don't know if this will be at all helpful. But I just have to say, I think that idea is ... I don't know much of anything about virology, or science in general for that matter, so I don't know if this will be at all helpful. But I just have to say, I think that idea is awesome.
I was just mostly skimming this thread because I'm so busy this week, but that caught my eye. It sounds like someone needs to write some fiction with that idea in there at the very least.
How could you test this theory of yours?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=253592#Comment_253592 2010-08-05T12:59:01-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 @Fishelle Thanks! I come up with a lot of scientific ideas I'd like to use in my fiction, but with biology it's typically pretty hard to work them in. "Viruses are an ancient means of ...
Thanks! I come up with a lot of scientific ideas I'd like to use in my fiction, but with biology it's typically pretty hard to work them in. "Viruses are an ancient means of cell-cell communication" needs a bigger idea before it can get worked into a whole plot. Though, if anybody has ideas, I'd love to co-write something involving my theory.

The smoking gun would be to discover a virus that has some beneficial effect on its hosts, in terms of a genetic enhancement. Basically, if there's a virus that does naturally-occurring gene therapy, that's a strong argument for my theory. But it's hard with experiments on origins to show anything other than "this idea is possible." Nobody was there, so it's hard to say "this happened." The best you can do is either showing proof of concept or ruling out alternatives.

There is some evidence that the existence of genome-altering viruses like HIV has a positive effect on a species' fitness, though. So in a way that supports my idea.

I think it would take a lot of effort (might be possible, though) to rule out enough alternative options to say that any one theory of viral origins is "the" theory.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=255814#Comment_255814 2010-08-17T21:55:04-07:00 2010-08-17T21:57:01-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I thought I'd share this blog post from Virology Blog. It's about a new book called INSIDE THE OUTBREAKS, which documents the activities of the Epidemic Intelligence Service of the US Centers for ... this blog post from Virology Blog. It's about a new book called INSIDE THE OUTBREAKS, which documents the activities of the Epidemic Intelligence Service of the US Centers for Disease Control. The cover is set up to be comic-book style, but I fear the inside is not so much. However, it does contain a bunch of exciting anecdotes and highlights from the EIS's history...it's not really supposed to be a chronology, more of a collection of "war stories."

Either way, the EIS is one of the most interesting things around. They're the guys who are on-site when there is a disease about and you don't know what it is. I know a few people who have gone through the training program, and they've all come out with some solid, real-world experience. Students with an interest in virology might want to try this one out.

Anyhow, enjoy. I'll probably pick up a copy of this myself eventually.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=255829#Comment_255829 2010-08-18T01:49:28-07:00 2013-05-24T22:37:42-07:00 Seantaclaus http://freakangels.com/whitechapel/account.php?u=6498 @John Skylar - I really dig this thread, and appreciate that you're taking the time to discuss Virology with us. It's rather eye-opening, and quite interesting, to say the least. Thank you. John Skylar - I really dig this thread, and appreciate that you're taking the time to discuss Virology with us. It's rather eye-opening, and quite interesting, to say the least. Thank you.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=255992#Comment_255992 2010-08-18T23:08:59-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 Thanks so much, man. It's nice to share this stuff with so many people who look at a thing from so many different angles. I can't think about Virology a million different ways, and neither can ...
And I don't know if y'all can get this paper because it's not open access, but I find it too fucking interesting not to mention, from the Journal of Virology, today. It's about the structure of one of the viruses that infects "extremophile" archaebacteria, which live in crazy inhospitable places. If we're to colonize other planets, we've a lot to learn from Archaebacteria and the viruses that infect them. This paper gives us the structure and stability of one such virus, which is a step in the right direction to understanding how such fragile, tiny things can survive in the harshest places.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=263808#Comment_263808 2010-10-07T15:45:52-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 Two updates for you, Whitechapel: One! I have heard some things about bees and colony collapse disorder. The big controversy was over whether bee colonies were dying because of a fungus or a ...
One! I have heard some things about bees and colony collapse disorder. The big controversy was over whether bee colonies were dying because of a fungus or a virus. Today, PLoS ONE (normally kind of a junkpile journal, really) had an article answering the question: It's both! Apparently a fungus from genus Nosema and a virus from the family Iridoviridae ("Iridescent Viruses") work together to kill bee colonies. Now, perhaps, we can work to save the bees.

...also, I want to write some kind of story with a character named "Iridescent Virus."

On another front, perhaps less significant, a question that I've been wondering about for two years was answered in today's PLoS Pathogens (not a junkpile). Retroviruses (like HIV) package two copies of their genomes, whereas other viruses package only one. No one knew why, but this paper suggests it helps the virus tell its genome apart from other RNAs inside the cell, and also helps the virus resist irradiation. So, clearly, retroviruses are ready to go with us into space.

That question really bugged me for awhile, it's nice to see it answered.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=263983#Comment_263983 2010-10-08T13:33:48-07:00 2013-05-24T22:37:42-07:00 roadscum http://freakangels.com/whitechapel/account.php?u=7712 John, thanks for the updates. Keep it up mate. Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264080#Comment_264080 2010-10-09T07:53:38-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 On closer inspection, and in light of this article, I'm going to say that CCD isn't necessarily a solved problem. It seems that there is a good reason that the article was in PLoS ONE, in light of a ... this article, I'm going to say that CCD isn't necessarily a solved problem. It seems that there is a good reason that the article was in PLoS ONE, in light of a somewhat weak last figure and the fact that there is a controversy over the effect of pesticides on the bees.

The numbers still suggest that iridovirus and Nosema in combination are involved in CCD. But that doesn't mean that susceptibility isn't caused by pesticide exposure.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264111#Comment_264111 2010-10-09T13:46:43-07:00 2013-05-24T22:37:42-07:00 roadscum http://freakangels.com/whitechapel/account.php?u=7712 An inconclusive article (Quote: the research does not "clearly define" whether the concurrent virus and fungus... is "a marker, a cause, or a consequence of CCD.") by a researcher ...
Reading through the article, it looks to me like Bayer are involved in a desperate attempt at some serious arse covering.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264431#Comment_264431 2010-10-11T21:27:29-07:00 2010-10-11T22:11:52-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 Well, the news article is really sensationalist, to be fair. Scientists are a little more restrained, so I'll try and present why this is reason to doubt, not reject, the paper. For one, while ...
For one, while the lead author (usually not the most experienced or notable scientist on the list) appears to have taken funding from Bayer at some point in the past, there is no evidence that any of the other authors (and there are 16 of them) had a conflict of interests. Furthermore, these people are at a variety of institutions, none of them affiliated with Bayer. So, don't believe everything journalists say. I'm not willing to reject this paper outright simply because one of its authors has a questionable connection in his past.

Furthermore, the paper does pretty much get the smoking gun on the IIV/Nosema connection to CCD. The way that we assess if something is the causative agent of a disease is via a set of rules called Koch's Postulates. If they're satisfied, then we are willing to say that the disease is caused by the infectious agent in question.

The paper appears to satisfy all four postulates, so it does seem to have found the cause. However, the satisfaction of postulate #3 is not demonstrated as independent of pesticide exposure. All they needed to do was test the bees for exposure to Bayer pesticides, show that there was none, and then include that as a supplementary figure. They probably didn't do that because they didn't want to pay the figure fees, and the reviewers didn't ask for it.

I expect a paper from this group, sooner or later, that shows that bees that are totally naive to pesticides will still get CCD when exposed to IIV/Nosema. If that paper doesn't turn up, then you can start to suspect fishy things.

And if any of the authors retracts their name from the paper, then you can really suspect fishy things.

Until then it seems like the paper is okay, but that it could use a little bolstering and outside confirmation. I would not, however, say that the paper is invalidated.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264673#Comment_264673 2010-10-13T07:38:59-07:00 2013-05-24T22:37:42-07:00 Lucid Seraph http://freakangels.com/whitechapel/account.php?u=9441 Ah, the bee issue. I somewhat suspect that CCD is an excessively complicated thing. Still, this stuff seems to indicate progress, which is great. (This thread is lovely by the way, and much more ...
(This thread is lovely by the way, and much more interesting than pedagogy, which is what I am supposed to be doing)

re: viruses as a form of communication gone horribly wrong... John, I talked to you over AIM about a few ideas on how to turn that into a plot, but unfortunately the only thing I can think of at present is using it as a backstory for a thing about superheroes/metas/mutans/what have you. Or possibly a virus as a vector for a beneficial mutation, something that evolved for species-wide survival (I know, I know, Evolution Does Not Work That Way). Or a way to explain psychics in a different sort of plot. It doesn't seem to be a plot-thing on its own, however.

Interesting; in googling Mimiviruses I found out that apparently a mimivirus showed up in Rainbow's End as a form of mind control (according to Wikipedia); so not entirely a new idea, this plot kernel!

So, now an actual question; re Mimiviruses - I've heard theories that mimiviruses are a proto-cell, a precursor to what we'd call Actual Life. What's the deal with this theory? And how legit do you personally think it is? ('You' here meaning 'y'all biologists in this here thread')]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264848#Comment_264848 2010-10-14T10:26:59-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I was recently at a symposium, and I saw a poster that leads me to believe that this finding from March 2010 is going to be a somewhat big deal in the HIV field. I can't say more because I don't ... this finding from March 2010 is going to be a somewhat big deal in the HIV field. I can't say more because I don't think this poster's contents are published yet, but keep your eyes peeled.

tl;dr: Cannabinoids (like, say, THC) might interfere with the HIV life cycle.

PLEASE NOTE: This is not specific medical advice, but mention of a curious finding. None of you are to go running around saying it's okay to have unprotected sex with everyone you meet if you smoke pot, because that is NOT TRUE. HIV is still a killer, and pot still has drawbacks (but so does alcohol).

@Lucid Seraph

We spoke about mimiviruses up top. I wouldn't call mimiviruses a proto-cell by any stretch, because they lack the protein expression machinery that is needed in order to replicate themselves. That machinery is only found in an actual cell, so mimiviruses could not preexist cells as they need them in order to replicate. There's not much of a chicken-egg problem with viruses and cells because we know that viruses are obligate parasites. No cell means no virus. However, mimiviruses might qualify as as proto-virus, a degenerate parasitic cell that gave rise to later viruses. That seems to be a strange idea, to me, since the diversity of viruses on the whole is so much greater than the diversity of mimiviruses. But it's possible. I just don't know how to test it to my satisfaction.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264907#Comment_264907 2010-10-14T20:11:43-07:00 2013-05-24T22:37:42-07:00 Romeo http://freakangels.com/whitechapel/account.php?u=1799 This whole thread is fascinating. It's a great place to start for the biopunk comic I am working on, but honestly, comic and narrative set aside, this stuff is just fascinating period. Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=264934#Comment_264934 2010-10-15T04:33:30-07:00 2013-05-24T22:37:42-07:00 smileyfish http://freakangels.com/whitechapel/account.php?u=8832 Interesting stuff on retro-viruses there John Skylar. Thanks for posting it up! Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=266172#Comment_266172 2010-10-22T10:01:11-07:00 2010-10-22T10:01:34-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 (thanks @ smileyfish and Romeo) But also! Today, PLoS Pathogens is out, and it has an article entitled Social Media and Microbiology Education. It's written by Dr. Vincent Racaniello, who ...
But also!

Today, PLoS Pathogens is out, and it has an article entitled Social Media and Microbiology Education.

It's written by Dr. Vincent Racaniello, who does the Virology Blog and the This Week in Virology podcast, both of which I've plugged on here before. Dr. Racaniello is a big inspiration for me, and I think that he's a scientist to watch because he is very driven about using new media and new venues to improve science education. The zeal and enthusiasm that he has for teaching the world about Virology in new ways reminds me of how bold Mr. Ellis can be in terms of finding new and interesting means to serve content to comics readers. It's good that there are people like this in fields that I like to follow.

Anyway, it's not a technical article. It's Dr. Racaniello summarizing what he's learned from blogging, social networking, and podcasting in virology. I'm so glad to see this in print, and it's worth a read. I almost considered making a new thread for it but I didn't want to tempt an eely fate.

In some ways, the article is a guide to open science. In other ways it's a guide to social media marketing, and not in the "I want to sell consulting services" douchebag way, but in the "I want to make the world a smarter place" way.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=274638#Comment_274638 2010-12-14T09:08:31-08:00 2013-05-24T22:37:42-07:00 Finagle http://freakangels.com/whitechapel/account.php?u=5254 Forgive me for what may be a 101-level question, but: Can you folks point me to information regarding long-term effects of viral coexistence? The personal reason I ask is that I myself am ...
Can you folks point me to information regarding long-term effects of viral coexistence?
The personal reason I ask is that I myself am infected with Cosackievirus, having had Hand-Foot-Mouth as a child. I've been observing some viral resurgence over the years (occasional deep blisters on hands).

But beyond that, I am also interested in any possible link to psychological effects of long-term viral coexistence. I understand that recent research has shown, crudely, that it is possible for viruses to affect the behavior of the host in order to favor their reproduction. I am curious as to any research involving higher-order mammals and viruses such as the chicken pox virus or Cosackie.

Long story short - with such long-dormant viruses, is there any evidence that those classes of viruses can have any effect on human behavior?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=274643#Comment_274643 2010-12-14T09:55:48-08:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 DISCLAIMER: I cannot give specific medical advice. Anything that I say is scientific analysis and does not consider the potential implications for medical treatment, because I'm not a medical ...
I'll say offhand that studies of viral persistence and host-virus equilibrium are not where they need to be to fully answer your question.

Coxsackievirus is an ssRNA virus, so it falls into my realm of specialty, though as an enterovirus I'm slightly unfamiliar with some of its finer points. I will say that its ability to persist in fibroblasts and pancreatic cells is unusual among RNA viruses; most RNA viruses are bad at lasting in a host and are usually self-limiting.

Notable exceptions are Measles virus, Nipah virus, and Hepatitis C virus. Unfortunately the symptoms of all of these in their persistent form are not good things to have, however, Coxsackie virus does not appear to have the same long-term prognosis. When it comes to ssRNA viruses that you could have a persistent infection from, it's better than the alternatives.

And furthermore, there's some evidence that persistent viruses (namely HCMV and EBV) may actually help provoke a stronger immune response against other viruses, so I won't say that persistent infection is universally a bad thing. Chicken pox virus, also known as Varicella zoster, is a DNA virus related to HCMV and EBV. Its only known persistent issue is reactivation under stress to cause the disease known as shingles, which is neuronal but is not behavioral. It's not related to ssRNA viruses even a little.

When it comes to potential effects on your behaviour or personality, I doubt that coxsackieviruses would be responsible. Unlike their cousin, Polio virus, Coxsackieviruses are very unlikely to infect the central nervous system, and when they do it is usually during initial infection and leads to encephalitis. I'm not ruling out some more complicated situation, but I think you really don't have to worry about that on a personal level.

On a more general level, this is a pretty interesting question. My biggest question with respect to this is how Rabies virus can cause hosts to exhibit hydrophobia--literally fear of water--and whether or not this is helpful to the virus in some way.

There are two long-term viral related psychological symptoms that I know of. One is the apparent correlation between maternal influenza virus infection (or cat ownership, incidentally, hinting at a toxoplasmosis relation as well, but we already know that's a neurotropic parasite) and later development of schizophrenia. And we're not even sure that's caused by influenza virus, nor is it a very strong correlation.

The other is a long-term symptom of end-stage HIV infection, which is a horrible psychosis that some HIV patients develop...that's not the most common symptom in the universe, either.

So tl;dr: no, there isn't much evidence that persistent RNA virus infection can have psychological symptoms, except for very specific viral infections (Rabies and HIV, specifically). Coxsackievirus has one disease associated with persistent infection, and that's diabetes. Talk to your doctor about that, but it's no guarantee that coxsackievirus infection leads to diabetes. If you're concerned about this as an intellectual question, then my answer should be enough. If you're concerned about it as a personal medical issue, please instead speak to a medical doctor as they will have a better idea about what causes certain symptoms, and whether or not it is a virus. I only know how viruses drive their symptoms; MDs know which causes, viruses or otherwise, drive the various combinations of symptoms that people can have. My knowledge is intentionally specialized and will therefore have many gaps with respect to what non-viral things might cause a given symptom.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=274651#Comment_274651 2010-12-14T11:00:39-08:00 2013-05-24T22:37:42-07:00 Finagle http://freakangels.com/whitechapel/account.php?u=5254 Great stuff, and all caveats taken in the spirit they were given. I'd love to hear more in general on this topic, if folks feel like elaborating on such. I'd love to hear more in general on this topic, if folks feel like elaborating on such.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=274870#Comment_274870 2010-12-15T14:37:43-08:00 2010-12-15T14:41:56-08:00 BOODOFFSTAGE http://freakangels.com/whitechapel/account.php?u=914 Just in case, you havent visited Warren Ellis's site. Article on first HIV infected patient to be cured. Although, the current cure sounds elaborate, expensive, unpredictable and hard on the ...
http://www.aidsmap.com/page/1577949/]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=274977#Comment_274977 2010-12-16T11:33:02-08:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 This "cure" thing is kind of old news, really, since the publication showing his status of no virus and high CD4+ cells came out about a year ago. The big deal about this is that he's ...
The big deal about this is that he's still cured now, so the scientists are willing to start using the word "cure." Great, but it's basically what we all expected when they showed he hadn't died.

What's really going to be important will be to see if he doesn't get cancer from the treatment a few years down the line.

At any rate, it's truly exciting research. Still, not going to help people in Africa with their HIV infections. At least not for many decades, at the pace of medical approval.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286280#Comment_286280 2011-03-10T11:52:03-08:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I don't know if you guys can see the actual paper (can't remember if Nature has a paywall or not), but here's the title: "Cocaine Analog Coupled to Disrupted Adenovirus: A Vaccine Strategy to ...
"Cocaine Analog Coupled to Disrupted Adenovirus: A Vaccine Strategy to Evoke High-titer Immunity Against Addictive Drugs"

That's right. Using viruses with coupled small drugs to actually create an immune response against those drugs so they don't get the addict high anymore.

There's been some work done already with anti-cocaine antibodies, but that only lasts about six months. This vaccine, based on a common virus, would provide protection from addiction for life.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286310#Comment_286310 2011-03-10T16:06:55-08:00 2013-05-24T22:37:42-07:00 Fan http://freakangels.com/whitechapel/account.php?u=6919 > protection from addiction for life I don't know; maybe not. Don't people get addicted to lots of things simultaneously: you know, drink, cigarettes. drugs, gambling, etc.? Doesn't that ... protection from addiction for life

I don't know; maybe not. Don't people get addicted to lots of things simultaneously: you know, drink, cigarettes. drugs, gambling, etc.?

Doesn't that imply, that it's not the particular substance, but that (those) people have a vulnerabiity to any kind of substance abuse: maybe poor impulse control, diminished incentives to be sober, maybe environmental, educational, and social/role-model factors too: who knows.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286312#Comment_286312 2011-03-10T16:33:03-08:00 2013-05-24T22:37:42-07:00 Artenshiur http://freakangels.com/whitechapel/account.php?u=8804 Two points there, Fan. First, you're confusing psychological and physiological addiction. You can get psychologically addicted to anything you like, but physiological addictiveness varies by ...
Second, the vaccine prevents not only addiction, but the drug's effect in the first place. You can't get high on cocaine once you've been inoculated. Sure, you might get addicted to sniffing powder, but that's significantly less bad for you. And remarkably unlikely.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286337#Comment_286337 2011-03-10T21:19:02-08:00 2013-05-24T22:37:42-07:00 Kosmopolit http://freakangels.com/whitechapel/account.php?u=1346 I suspect some people would shift to snorting other psychoactive dugs. Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286340#Comment_286340 2011-03-10T22:12:07-08:00 2013-05-24T22:37:42-07:00 BrianMowrey http://freakangels.com/whitechapel/account.php?u=1709 That kind of blows my mind. Cocaine is not a big molecule and it is lighter than sucrose. How do you make your neuron receptors capable of blocking something that small without fucking up a larger ...
That's not really a virus question though. And the article was paygated so I've only read the abstract. Did they measure negation of cocaine's effect in any matter other than how much the mice moved around? Maybe the mice were still feeling good but just in a mellow way. Cocaine like everything that touches a protein has more than one pathway. Just thoughts.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286395#Comment_286395 2011-03-11T06:51:28-08:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I don't know; maybe not. Don't people get addicted to lots of things simultaneously: you know, drink, cigarettes. drugs, gambling, etc.? Well, I meant cocaine addiction alone. Gambling isn't ... I don't know; maybe not. Don't people get addicted to lots of things simultaneously: you know, drink, cigarettes. drugs, gambling, etc.?

Well, I meant cocaine addiction alone. Gambling isn't going to be something we can really make a vaccine against, but artenshiur's right that there are different types, and different levels, of addiction. Cocaine and crack are very difficult habits to break because of their inherent qualities as dopamine agonists. Even people who want to get clean have a lot of trouble doing so. This vaccine provides another tool to help them.

However, just a note about cigarettes: I have heard of some work being done to make antibodies to nicotine, similar to this. We'll see if it goes anywhere.

I suspect some people would shift to snorting other psychoactive dugs.

The key part here is the "some." If this works to help some people get clean from a drug addiction that's hurting them, it's fulfilled its purpose.

But, remember...the same vaccine strategy that worked for cocaine could work for other drugs as well.

Did they measure negation of cocaine's effect in any matter other than how much the mice moved around? Maybe the mice were still feeling good but just in a mellow way.

There isn't really a way to measure mouse emotions, just behavior. Still, the mouse response to cocaine is well known, and this kind of antibody vs. cocaine treatment has been tested in humans before. Instead of a vaccine in that case, it was just a prepared antibody, so "immunity" was not permanent, but it definitively reduced the potency of the high. That effect in humans corresponded to the same changes in mouse activity that were observed in this paper.

When they say they measured how much the mice moved around, they don't mean a small effect. Looking at the figures, the mice that were high ran all over the area like frenetic little junkies for the duration of the experiment. The mouse trackers are almost black with the tracings of their routes. The control mice, like all normal mice should, hugged the sides of the enclosure and moved far less. It's such an extreme effect that it seems pretty clear that one group of mice was high, and the other was not.

How do you make your neuron receptors capable of blocking something that small without fucking up a larger process?

I saved this for last because it's a cool question.

The thing about this strategy is that it uses the antibody response. By using antibodies, it can get the cocaine to be pulled out of the bloodstream before it ever reaches the brain, and so there doesn't have to be any interference with normal neural processes. The brain is, so to speak, surrounded by friends in the bloodstream who take away its keys so it doesn't make a mistake.

Also, because it's an antibody response, it's specific to cocaine and cocaine alone. Antibodies are cool like that.


Finally, one point that some of my colleagues brought up is that this could lead addicts to just try and take more cocaine in order to overcome their immunity. While that's true, after every challenge to the immune system on a specific antibody response, there's a jump in the level of that antibody. So if I try to get high one night and it doesn't work, then I take double the next night, the spike in my antibodies might prevent that too.

The problem is...if I keep trying too hard, I might take way too much cocaine and die, either from an extreme immune response, almost like an allergic reaction, or from the cocaine itself. That problem *should* be mitigated by the antibodies, which ought to keep the cocaine from damaging anything, but since they didn't test OD dosages on the mice, we don't really know.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286481#Comment_286481 2011-03-11T19:55:17-08:00 2013-05-24T22:37:42-07:00 Fan http://freakangels.com/whitechapel/account.php?u=6919 By using antibodies, it can get the cocaine to be pulled out of the bloodstream before it ever reaches the brain, and so there doesn't have to be any interference with normal neural processes. I ... By using antibodies, it can get the cocaine to be pulled out of the bloodstream before it ever reaches the brain, and so there doesn't have to be any interference with normal neural processes.
I see. That is cool.

Do you have any idea what the smallest molecule is that could be targeted: alcohol?

By the way, did you know, on the subject of 'impulse control': sometimes, a Parkinson's patient wants to tell their body to do something, but it doesn't do it (so they're unable to do that). To counter-act that, a typical Parkinson's med is a dopamine agonist: for which, the side effects can include excessive shopping, gambling, etc.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286596#Comment_286596 2011-03-12T20:11:08-08:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 Do you have any idea what the smallest molecule is that could be targeted: alcohol? That's pretty complex, actually. Antibody targeting isn't easily understood and there are still a lot of open ... Do you have any idea what the smallest molecule is that could be targeted: alcohol?

That's pretty complex, actually. Antibody targeting isn't easily understood and there are still a lot of open questions. You tend to hear people throw words around like "heft" or "bulk," because the size of the molecule doesn't seem 100% important, it's more like a combination of volume and mass, so something like "density." I'd call cocaine a pretty hefty small molecule.

Alcohol's real tiny though. I honestly don't think anybody knows what the definitive answer to this would be, which to me means you've just found an experiment that needs to be done.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=286599#Comment_286599 2011-03-12T20:43:14-08:00 2011-03-12T20:47:01-08:00 BrianMowrey http://freakangels.com/whitechapel/account.php?u=1709 Finally, one point that some of my colleagues brought up is that this could lead addicts to just try and take more cocaine in order to overcome their immunity. Or put a tube in their skull to ... Finally, one point that some of my colleagues brought up is that this could lead addicts to just try and take more cocaine in order to overcome their immunity.
Or put a tube in their skull to inject cocaine directly behind the blood-brain barrier? *Edit actually I am going to go ahead and use the subsequent story idea I added to this comment, nvm*]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306285#Comment_306285 2011-08-15T11:53:15-07:00 2013-05-24T22:37:42-07:00 256 http://freakangels.com/whitechapel/account.php?u=4827 @John - this might not be sufficiently exotic to warrant resurrecting the thread, but I wondered if you had any comment on MIT's release about a general-purpose anti-viral drug. Is this really ... @John - this might not be sufficiently exotic to warrant resurrecting the thread, but I wondered if you had any comment on MIT's release about a general-purpose anti-viral drug.

Is this really radical and game-changing, or more like an incremental improvement? It's always hard to get a good picture outside your own field. Any speculative consequences of a Whitechaplain nature?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306289#Comment_306289 2011-08-15T12:22:50-07:00 2013-05-24T22:37:42-07:00 RenThing http://freakangels.com/whitechapel/account.php?u=155 @256 I wondered about that article because it seemed to cause almost as a kerfluffle among my friends list as that idiotic "Scientists cure cancer and NO ONE TOLD ABOUT IT" post that ...
I wondered about that article because it seemed to cause almost as a kerfluffle among my friends list as that idiotic "Scientists cure cancer and NO ONE TOLD ABOUT IT" post that went around a few months back.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306291#Comment_306291 2011-08-15T12:25:45-07:00 2013-05-24T22:37:42-07:00 BrianMowrey http://freakangels.com/whitechapel/account.php?u=1709 It should be a legit important thing. With antibiotics, for example antibacterials, the trick is finding a place in the bacteria's workflow that makes a unique marker and homing in on that for the ...
With antibiotics, for example antibacterials, the trick is finding a place in the bacteria's workflow that makes a unique marker and homing in on that for the attack. The limitation is that the not all bacteria have the same workflow, and finding molecules to hit just that process without side-effects is expensive and hard, and bacteria are mega hardy even aside from selection-based resistance.

For dsRNA, the perfect detector molecule that activates on contact is already something our cells have been making all this time. The MIT drug, by their report, doesn't need to do the heavy lifting, it just straps a bomb onto the mechanic.

The big question is: why does our immune system have a device to intercept viruse workflow with 100% efficiency that was leading to a weak defense process instead of agressive cell destruction? Our cells have some splaining to do :(]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306306#Comment_306306 2011-08-15T14:26:05-07:00 2013-05-24T22:37:42-07:00 Nygaard http://freakangels.com/whitechapel/account.php?u=431 @BrianMowrey I have vague recollection of someone claiming that 100% immunity is generally not selected for - the evolutionary pressure is actually toward partial immunity; can't even remember if ... Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306312#Comment_306312 2011-08-15T15:03:57-07:00 2013-05-24T22:37:42-07:00 BrianMowrey http://freakangels.com/whitechapel/account.php?u=1709 You might be right. On the other hand we aren't aware of it, but our immune system already includes some total warfare stuff built in. For example, in a microscopic environment one of the most ...
On the other hand we aren't aware of it, but our immune system already includes some total warfare stuff built in. For example, in a microscopic environment one of the most important concerns of a cell is iron acquisition. If a bacteria is floating around in our blood, it needs to get iron or can't be productive. When our bodies go into immune response, our liver chemistry changes and iron becomes immediately scarce. So by default, are a harsh and awful environment for bacteria to grow in. But lots of bacteria have amazing kung fu iron-stealing technology already. Our blood is like a desert and bacteria are like irrigation farmers. So we still get sick. My point just being, the immune system isn't pulling any punches on the iron resource front.

So why is it phoning it in with dsRNA response? From the MIT article, we learn that the dsRNA targetor sets off a complicated defense mechanism that many viruses know how to block. Why such a shitty defense? It is an intersting question maybe.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306329#Comment_306329 2011-08-15T18:34:31-07:00 2011-08-15T18:36:23-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I was debating sharing that paper in this thread, but I have serious reservations about it. What they have done here is quite remarkable. This is in my field, as I generally focus on host sensing ...
What they have done here is quite remarkable. This is in my field, as I generally focus on host sensing of viral RNA. I think it's quite courageous of the authors to call this a therapeutic, however.

It's a protein, not a small molecule. That's a big deal in drugs. It means it can't be delivered orally, for one thing. It probably can't even be delivered in the bloodstream. Your body could also potentially see it as a nonself molecule and make you immune to its activity (though I believe they have skirted that issue).

So, you can see that the mice in this paper had to be injected intraperitoneally in order for the thing to work. That's disappointing. I don't personally want to get gut-stabbed any time I have an RNA virus infection. Now, for something like Ebola, I'd take the gut shot. Rhinoviruses I think I'd wait out.

Furthermore, viruses readily evolve defenses against just this kind of killing mechanism. Escape mutants (read: resistant mutants) are probably easy, as the proteins that they used are just bits of host proteins stapled together with recombinant genetics.

So it's weak to escape mutants, difficult to impossible to deliver, and it uses a mechanism that many viruses can already evade effectively. I don't give this a lot of points for calling itself a "therapeutic." It's an interesting proof of concept, though. Now what they really need is a small molecule that activates the same pathway but during a virus-specific condition.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306334#Comment_306334 2011-08-15T19:10:51-07:00 2013-05-24T22:37:42-07:00 BrianMowrey http://freakangels.com/whitechapel/account.php?u=1709 It's a protein, not a small molecule. ... It's an interesting proof of concept, though Exactly. Like how in antibacterials, every targetable process is a potential array of drugs grouped by action ... It's a protein, not a small molecule.
...
It's an interesting proof of concept, though
Exactly. Like how in antibacterials, every targetable process is a potential array of drugs grouped by action mechanism, the advent of DRACO is also the advent of later things that have a better way of doing the same thing. Right?

Yayyy

What was really news to me though was the article said all animal viruses have a dsRNA production stage -- because, that's a broad spectrum action mechanism just by definition. I usually glaze over the molecular part of the textbook when I am pretending to be a biology student, but I know viruses have lots of variety in what format they choose to store their code in in their actual virons. I had never read anything about them universally using dsRNA during replication. But are you saying it would be easy for animal viruses to workaround that? Or, that actually lots already don't need a dsRNA stage for replication, and the article exaggerates the broadness there?]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306339#Comment_306339 2011-08-15T20:13:29-07:00 2013-05-24T22:37:42-07:00 Artenshiur http://freakangels.com/whitechapel/account.php?u=8804 @Brian, I'm no expert, but just off the top of my head it doesn't seem necessary for a virus to circumvent the dsRNA stage to develop a resistance to DRACO if, for example it can inhibit apoptosis. Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306342#Comment_306342 2011-08-15T20:48:01-07:00 2011-08-15T20:50:48-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 If this is the first step of a new class of antivirals, they will either have to be small molecules that activate an extant DRACO-like protein (unlikely, but possible) or there will have to be some ...
To address more, I'd say it's not strictly true that all animal viruses have a dsRNA stage. There is a paper that says DNA viruses produce dsRNA species through some weird RNA polymerase III-mediated mechanism, but...I dunno. That idea has always seemed weird to me, and it's a pretty new idea anyway.

Artenshiur has a point that viral evolution tends to involve the quickest path to resistance (I was tempted to say "path of least resistance" but then realised that this analogy might be very confusing). I was referring to evolving an inhibitor of apoptosis, or an inhibitor of DRACO itself. Most animal viruses already have proteins that inhibit things like the proteins that inspired DRACO, so it wouldn't be very difficult (well, I imagine it wouldn't be) for those proteins to evolve a broader specificity and function against this construct.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=306544#Comment_306544 2011-08-17T11:41:16-07:00 2013-05-24T22:37:42-07:00 256 http://freakangels.com/whitechapel/account.php?u=4827 Cheers for the comments, John - always good to hear from someone who knows their stuff. Depressingly, the nuttery has begun.
Depressingly, the nuttery has begun.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=309419#Comment_309419 2011-09-15T11:17:49-07:00 2013-05-24T22:37:42-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 So, anybody seen CONTAGION? Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=309487#Comment_309487 2011-09-16T03:59:17-07:00 2013-05-24T22:37:42-07:00 J.Brennan http://freakangels.com/whitechapel/account.php?u=1028 @John: I saw Contagion the other day. I went with friends and hadn't heard anything about it besides the name. I was pleasantly surprised that it wasn't another Outbreak. It felt far more ... TED Talk on preventing pandemics via AICN of all places while reading a couple interviews with the director and writer.

I'd like to say I found the Jude Law character a bit of an overly heavy-handed swipe at anti-vaccination proponents, but given what the CDC has been documenting lately I don't think that swipe can be too heavy at all. Rather frightening when thinking about some of the nastier things that are normally vaccinated against.

But my opinion is that of a layperson, I'm very curious about what people in the fields portrayed thought of it.]]> Exotic Virology http://freakangels.com/whitechapel/comments.php?DiscussionID=8634&Focus=309518#Comment_309518 2011-09-16T10:47:31-07:00 2011-09-16T10:56:07-07:00 John Skylar http://freakangels.com/whitechapel/account.php?u=8976 I felt that while all of the science occurred at movie-speed, it was the most scientifically accurate and realistic portrayal of such an event that I've ever seen. I happen to study the virus that ...
I happen to study the virus that the movie's MEV-1 was modeled after. It's called Nipah virus, and basically, this movie could have happened when it first appeared in 1999. It would've worse than in the film, then.

While they sped up the science in the movie, they also sped up the virus. Nipah virus can have about a week of incubation period, as well as two weeks of profoundly horrible disease before either resolution or death (in 40-70% of cases). However, Nipah doesn't display sustained human-to-human transmission. Thankfully.

I think Jude Law's character was an accurate portrayal of the kinds of people who pop up around genuine information about virology all the time. There's always someone out there who was once looking for answers, but then latched onto the answer that stood to benefit them the most. They are either fooling themselves, or aware of it, and either way they end up playing to people's fears. There were people who advocated that Chronic Fatigue Syndrome patients should take anti-HIV drugs when one study said a retrovirus similar to HIV might maybe cause CFS (this was later found to be a lab contaminant). There were people who said you should overload your body with zinc when you get a cold because one study showed zinc could kill rhinovirus in a tissue culture dish (later, it didn't work in mice). There is a measles virus epidemic (incidentally, measles and nipah viruses are somewhat related, sequence-wise) in the UK because parents believed it would cause autism (disproven by numerous studies). Measles virus has a reproductive coeffcient (r-naught) of 15, and you can get it by being within 100 feet of a patient. All of these things are damaging, dangerous, and harmful, not just to the patient but to others around them. They are also all refuted by science.

But there is no science that can compete with the heartrending emotions of a mother toward her child, or the basic instinct that encourages you to take control of your life when you feel it's threatened. And because of that, this sort of person will always be looking for answers, and the ones who don't find those answers in science, will find them in all the wrong places.]]>