The progression of HIV in the human body was a mystery for a long time. It sits in your body for years, not doing much, then suddenly it takes over your immune system and BAM!---you have AIDS. (The actual sound it makes when it reaches this point is unclear.) Pictorially, the process looks like this:
The red line represents the amount of disease in your body. When HIV is first contracted, the amount of virus shoots up dramatically, but then decreases sharply as the immune system responds. The virus load then stays at a small level, increasing only gradually, until the mysterious trigger happens and it shoots up again, this time impervious to immune responses. The upper blue line represents the amount of CD4 cells in your body, which are the immune cells that HIV attacks. (The slide is stolen from Martin's lecture.)
The question, then, is what is HIV doing in the long "asymptomatic" phase, and how does whatever it's doing enable it to suddenly explode after such a long time?
Nowak gave a surprising answer in a 1999 paper: it is evolving.
The idea is that when a person is first infected, they have only one strain of the disease in them (i.e. whatever strain they got from whoever transmitted it to them.) The immune system can handle this: it makes an antibody designed to attack that strain, at beats it back down to a miniscule level. It can't kill it completely though, because HIV can hide in healthy immune cells.
Now, while HIV is hiding in plain sight, it's also reproducing and mutating at a very high rate. Once it's mutated enough, the antibodies can't recognize it, so different antibodies must be produced to contain it. This processes continues and the disease becomes more and more diverse within you.
But there's a limit on the number of different campaigns your immune system can wage at once. Nowak found a mathematical diversity threshold--i.e. a critical number of strains of the virus, beyond which the immune system can't deal with all of them at once (though any one of them at a time would be fine.) And then, BAM!
I found this fascinating because, while we all know the power of evolution to produce remarkable organisms, we don't usually think of this process happening within our own bodies. Also, this hints at the difficulty of finding a cure for HIV, since it is specifically designed to mutate its way out of trouble.
i took a class in evolution in college, and since aids evolves like it does, through natural selection it slowly becomes immune to the drugs that try to fight against aids. because of this, drugs versus aids work well for awhile, but slowly get worse.
ReplyDeletesomething interesting about that, though, is that they did an experimental treatment where they simply took patients off of medications, and as the immune-part of the aids virus started to lower in frequency while the non-immune took over, then put the patients back on the drug and it worked well again.
very interesting.
Actually that makes sense.
ReplyDeleteEvolving to a resistant form involves evolving to a form that requires additional energy and resources to enable it to be resistant.
The lower energy species/strain solution would be to forgo any non-essential, yet energy consuming metabolic processes not specifically required for survival. The extra energy of resistance creates a burden when not required which the low energy susceptible version can exploit to reproduce with less energy and resources (as commandeered cell parts) thus allowing more new viruses to be produced per cycle.
By removing the treatment for a time, the non-resistant variety suddenly has the survival advantage over the more energy-consuming resistant variety.
One has to wonder how many other familiar diseases work this way.
There is already evidence that livestock treatment with antibiotics is the evolutionary stress trigger for DNA conjugation transfer between E. coli and Shigella causes the creation E. coli O157:H7 (the famous meat food poisoning killer).
http://jmm.sgmjournals.org/cgi/reprint/49/7/583.pdf
http://svmweb.vetmed.wisc.edu/pbs/zoonoses/O157DT104/O157DT104index.html
Yeah, that's pretty logical, if there is a cost associated with drug resistance.
ReplyDeleteThe interesting thing to me is that, accoriding to Nowak's theory, when HIV is fighting your immune defenses, it's not just looking to develop one immune-resistant strain, but a variety of different simultaneous strains, each of which could be dealt with on its own.
So the mechanism used by HIV to fight your immune system (fast evolution) has the side benefit of making the disease virtually uncurable by drugs.
@Cassandra- that's very interesting about the evolution of E Coli under antibiotics. One of my current projects involves fast evolution of bacteria under changing environments. I'll try to get around to posting about it soon.