With the AIDS-causing HIV, you have to play it on its own turf and beat it at its own game.
HIV is a very successful virus in evolutionary terms; it is a wonderful survivor and has evolved faster than anything else known in the biological world. This rapid evolution has been the secret of its success. It can churn out 100 billion (!!) of its own kind within 24 hours! At this staggering rate of multiplication, it is no wonder that it can outpace any other creature in the evolutionary arms race. That’s not all! HIV has another trick up its sleeve it copies its genetic material with huge amounts of errors. True, the process is wasteful, but given the sheer number of individuals, HIV is sure to produce several healthy individuals, ensuring its own survival and changing too rapidly for the hosts’ immune system or medical R&D to catch up to it. This is, in brief, the problem that researchers currently face.
Chink in the armor
However, there’s some good news. There are some sites in the HIV proteins that tend to stay the same. Researchers hope to target these conserved sites’. This will lead to the virus losing some important part of its genetic material and, hopefully, losing out on the ability to reproduce. The bad news is that HIV can evolve so as to demote these sites in importance and thus escape annihilation.
A stunning insight following a crucial discovery resolves this impasse. Professors Arup Chakraborty and Bruce Walker (MIT professors) identified a large number of conserved sites and found that they were grouped together. This means that these sites are not isolated ones that are conserved; they are conserved en masse. Karthik Shekar and Vincent Dahirel, both geneticists at MIT, suggest that the immune system can be modified to attack these specific sites all at once. The idea is simple: HIV would have to undergo tremendous evolutionary mutations in order to mutate out of dependence on all these sites. This would definitely affect its reproduction abilities adversely.
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Exploiting the chink
Dahirel and Shekhar found that these patches of proteins evolve together. A protein that makes up the outer wall of the virus, called Gag, was their subject of interest. Gag carries five of these conserved sectors and they evolve independently. They further identified a sector amongst these named Sector 3 that was particularly conserved; it hardly evolved.
This conservation is essential for the virus as Sector 3 is crucial for the formation of the outer wall of the virus. Without it, it would be a naked collection of RNA strands.
Shekhar and Dahirel suggest that several sites in Sector 3 be targeted simultaneously. HIV would find it extremely difficult impossible, researchers hope to crawl its way through this evolutionary crisis. To do so, the virus would have to figure out some way to co-evolve all of these sites in exactly the same way so as to make each of the sites independent of each other and also unimportant in making the viral sheath. This amounts to finding a way around billions of years of evolution. Researchers hope that this will be an evolutionary blind alley.
Apparently, one in every three hundred people infected with HIV develop resistance and do so when their immune system adapts and attacks these Sector 3 sites. These HIV-positive people can live healthily for long without any medication. The trade-off is masterful: If the virus is to survive, it must do so in a weaker form, unable to cause the dreaded disease or reproduce as it normally does.
Walker, an expert in HIV immunology, says:
We need now to make immunogen with this new technique and see if this gets over the major hurdle we face in an HIV vaccine that of viral diversity and viral evolution to escape immune responses.
(Immunogens are clinical drugs that fire off extremely specific immune responses).
Predicting the next step
Taking this a step further is Joshua Plotkin and his group from University of Pennsylvania. They plan to map the evolutionary reactions of the virus when certain pressures are applied to them and predict the evolutionary future of the virus, in effect, deciphering the rules that govern evolution.
The game is on: It’s a cat and mouse game on the genetic scale with huge impacts on the human race. A new way to attack and cure (not just prevent) AIDS maybe around the corner.
Marvel at the wonder of evolution at work here!