Using Evolution Against HIV

One of the biggest difficulties for those trying to treat and prevent Human Immunodeficiency Virus (HIV) infection is its rapid evolution, even within one person.  Even though it was introduced in the mid 1990’s the drug Zidovudine is already slowing down in the fight against HIV as more strains are becoming immune to it.  However, scientists are now taking a new approach to HIV treatment and may use its high variability against it.

This approach relies not on viewing HIV as a pathogen to be eliminated but as a mobile immune system gene.  HIV is so deadly because, once it has infected its host, it inserts its DNA into the host genome and “blends in.”  We cannot target it for removal because it uses the same mechanisms as our own body to pass along its genes.  This would be fine if the virus had no effect and just stayed in the genome (in fact, some have proposed that as a mechanism of higher-organism evolution) but it does not.  HIV disrupts our bodies’ normal immune system and continues to replicate and spread, cluttering our genome with DNA that has no function for us. Zidovudine and other drugs like it target HIV before it has integrated itself into the human genome, when it is still in charge of its own replication.  However, once the virus has integrated itself into our DNA, these drugs are no longer effective and the virus can evolve protections against them.  HIV will most likely be able to evolve quicker than we can develop drugs to act on them.

But what if we could use HIV’s evolution against itself?  The fundamental problem with viruses such as HIV is that they hurt us, their host.  If they harm their environment, there is less room for them.  There is a constant balance for the virus to replicate itself as much as possible without killing its host before it can be transmitted.  If it leans too far towards replication, it kills its host and can no longer survive.  Scientists are now considering pushing HIV in the other direction: Forcing it to “play nice” with us and no longer impair its host.  Theoretically, a virus that is friendlier to its host will be less of a target for immune defense.  This would confer an evolutionary advantage to the “nice” HIV that may allow it to displace the current version entirely.  It is now up to science to design a virus that looks and acts like HIV but has none of the harmful effects.

This particular goal is not unrealistic.  Genetic modification in the lab is commonplace these days and the evolutionary potential of HIV makes it a particularly hardy specimen for this type of experimentation.   If HIV could be made relatively harmless in vitro (i.e. in a Petri dish in the lab, far away from living test subjects) the new virus may be a valid treatment option for those already affected with HIV.  If introduced into an HIV-positive person, the newly modified virus would compete with the other for dominance.  Because it is less harmful to its host, this new virus would be more fit (reproduce better) than the original virus.  Eventually the harmful HIV would be completely displaced.  The person would still be HIV-positive, but would suffer none of the harmful effects of the virus as it is now.  Interestingly, this treatment would continue to work with the current treatment options for HIV infection.  Both strains of the virus would be suppressed, but that would only help the new, harmless virus that is not being targeted by the body for elimination.

This approach stems from the evolutionary heritage of our current immune systems, in fact.  Our immune system genome currently has many non-functioning DNA sequences (last winter’s cold, for example).  It is the fact that these sequences are not harmful to us that allows them to continue to exist in our bodies.  These old genes may even be helpful to us if, for example, this winter’s cold is a mutation of last winters.  The only difference between the immunity components our bodies develop and the lab-modified HIV would be that the virus could reproduce outside of the cell.  The fact that there are some HIV-positive individuals that exhibit no symptoms of AIDS related illnesses points towards the fact that a mutual coexistence with HIV is possible.

The biggest obstacles, then, to developing this solution to HIV are social and economic in nature.  Medical systems are currently built around developing pharmaceuticals to combat illnesses and infections.  Using a virus against itself is, thus far, out of the realm of contemporary thinking.  It would require an entirely different approach on the part of scientists and health care providers.  Current HIV treatments work against its evolutionary strengths.  This new approach could use the viruses own strengths against it to fight a battle we are currently losing.

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~ by kevinpereira on December 17, 2009.

3 Responses to “Using Evolution Against HIV”

  1. I find it interesting that they are looking at these options in fighting the AIDS virus. In our biophysical chemistry, we looked also other methods of targeting AIDS virus. One method is inhibiting the action of proteases produced by the virus. Proteases are enzymes needed to digest proteins needed for the virus to function properly. Therefore, without the proteases the virus will not survive. The problem with problem, however, is that proteases mutate at a very fast rate. Therefore, inhibitors designed to target wildtype protease become ineffective against mutated versions. Some of the solutions proposed to avoid this problem is designing inhibitors with some sort of flexibility to make them effective against multiple versions of the protease mutated strains. They do this by making the inhibitors highly non-polar, which allows inhibitors to bind to the proteases with high affinity due to hydrophobic effect. However, the drugs are designed such that they are flexible in the active site.

  2. The source of the above comment: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TBN-4DH29MG-1&_user=5907928&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000068825&_version=1&_urlVersion=0&_userid=5907928&md5=bb06c5b2cdd61f6d740d6a5f982dc44c

  3. This novel approach to HIV treatment sounds theoretically superior the previous strategies that had to compete against the virus’s evolutionary mechanisms. I am unsure, however, just how injecting an innocuous virus into the host would decrease the rate at which the HIV virus was incorporated into the host genome. In other words, wouldn’t the host organism integrate BOTH the innocuous virus sequence AND the HIV virus into its genome?

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