Wednesday, August 31, 2011

The Philosophy of the Virus

Sorry for such a hiatus everyone. I've had serious changes I've had to adapt to, the chief being the first few weeks of medical school! In order to get away from the books that I have become slave to in the past couple of weeks, I am back. This time the topic of discussion is the virus. I've already written a short spiel about viruses that provided a brief theory about how viruses came to be (I encourage all readers to look at it again because it's awesome!) so I won't go there. This time I want to tackle an even bigger question that has grown more along the lines of philosophical debate than scientific inquiry. The question is simple "Do viruses think?"



The short answer to this question is "No." Okay great so post over, right? Not quite. There is more to the story of viruses that makes them seem more like living, thinking creatures more than they really are. So much so that the lines of biology start to blur the more you learn about them. Viruses are to the field of biology what black-holes are to physics. Once you closely inspect the underlining principles of the virus, the rules of biology start to break down and some really weird things happen that basically make you question the fabric of existence... Ok, so viruses aren't that crazy, but they do take part in some pretty crazy things.


Let's take for instance a virus we've all heard of before Rhabdoviridae...more commonly called Rabies. These things look like bullets, maybe its a grim premonition of what's to come once you've become infected. I think Rabies provides one of the most interesting examples of how viruses "think." Basically, Rabies virus has the unique ability among other virus to travel up neurons. This is pretty cool in itself because the cell actually transports it without ever knowing it's being infected! Eventually the virus reaches the blood-brain barrier which it breeches and infects the spinal cord and brain. This is where the virus starts to do something very strange. It starts to infect the cells of the salivary glands in the mouth, the cells that produce saliva. Not only this, but the infection of the neurons in the brains leads to severe agitation which can lead to an infected host biting an individual which can then spread the virus! So this is a case where the virus has evolved a mechanism of infection that plays off of a behavioral change caused by an earlier stage of the infection cycle.


This is such a profound manipulation of the host that movies like "The Crazies" have used Rabies virus as the basis for their viral outbreak. In fact there's a direct mention of Rhabdoviridae in the newest version of the movie. I laughed when I heard this and my friends had no clue what they were talking about. Authors and movie-makers even take this to another level by using the idea of "mutated Rabies" for the creation of zombies! Rabies on steroids would probably look something akin to those infected in the movies. It is the unique property of the virus to change the behavior of the host in order to continue its propagation that makes it the target of anyone wanting to create a fictional virus that has some basis in science...but more on that later... ;)


Is this virus really "thinking" about the best way to continue its own propagation? Of course you can just say "no," but then you'd fail to appreciate the true power of the virus. It's obvious to anyone that viruses can't think like us, but I think they have replaced "cognition" with the sheer power of evolution and biochemistry. Driven solely by these two processes viruses have developed their own way of "thinking" over billions of years.

Another example of these two processes at work can be found in the unique ways viruses replicate their genomes. Each class of virus has ways of achieving this in different ways, but I'll be general just to get the point across. Some viruses based on +RNA (essentially a coding strand of mRNA; the simplest virus possible) have built in genetic sequences that can form loops due to repeating sequences of bases. For instance a sequence of CAGCUG in RNA could potentially fold over in on itself and base pair to form a loop. Some viruses use these types of sequences to form loops which act on elongation initiation factor 4G (eIF 4G) within the host cell. The elongation factor recognizes the loop as a sequence that needs to be bound, completely unaware that it doesn't belong to the host. The elongation factor can then recruit the ribosome to begin translation of the viral genome. Basically the cell is translating the very proteins that are going to end up killing it! And let's not forget that coded within the genome are factors that essentially eliminate host cell translation and enhance viral translation even more!



Again we see that the virus is able to manipulate multiple ares of the cell in order to produce the biggest effect on its own replication cycle. Crazier still is that this virus would only be able to infect one specific type of cell, so the mechanism that I described is very selective for its target. This all comes from specific receptors that recognize certain host cells that the virus can exploit. It's incredible that such specificity can be achieved and so many ways of manipulation have been created by the virus.

Our cells are not stupid to the threat of viral infection either. As discussed in my very first post about the Red Queen Hypothesis, we have evolved a powerful set of immune system regulators. Our cells recognize some of the molecules produced by these viruses which are called Pathogen Associated Molecular Patterns or PAMPs. If one our immune cells binds a PAMPs it immediately begins a cascade of other signals that bring in nasty Natural Killer cells (yes, that is what they're called and they are pretty BA!), neutrophils, and plasma cells which produce antibodies. So what's the effect of the virus? They, in turn, evolve new ways of trying to evade these signals. They mask of their PAMPS by slightly altering their shape or eliminating the signals released by the cells. And back and forth the battle goes...



The complexity of viruses really makes you ask "How do they do that?" Yet they are still as primitive as they were billions of years ago. At their core they are only genetic material wrapped up in protein. Everything else about viruses, from the envelopes they use to shield themselves from recognition to the destructive signals they produce to kill their host are all the result over years of evolutionary change. So do viruses think? Or are they simply a byproduct of evolution? Either way it is for certain that they have developed ways of fundamentally changing our views of biology. This brings about a whole new meaning to a "smart" virus!