Tuesday, January 19, 2010

Host Restriction Factors: Intro

Now that I passed my qualifying exam it is time to get back to blogging. This post is going to be the first in a series about my thesis work on host restriction factors.

Under Pressure- Constant Retroviral Assault: One of the most potent driving forces behind evolution is selection pressure. There is no lack of evidence of macroscopic forces shaping the morphology of organisms, for example the convergent evolution giving sharks and dolphins similar shapes because the environment imposes the same hydrodynamic constraints. Similarly, microscopic factors, like viruses have shaped cellular evolution. Central to the survival of the cell, organism and species as a whole is the preservation of genomic integrity, a process retroviruses directly oppose. The human genome chronicles a long history of retroviral infection, exemplified by 8% of our genome consisting of endogenous retroviruses. This represents a finite percentage of all retrovirus-cell interactions, as these invaded the germ line, became inherited and preserved. Accordingly, some primate genes owe their present form to the intense selection pressure imposed by viruses.

The Red Queen- One can think of the interaction of viruses with the hosts they infect as an evolutionary arms race. The host wants to stay healthy so it can pass on its genes, while the virus wants to infect the host so it can copy its genome. Every time one gains the upper hand the other faces intense selection pressure. For example when a species gets better at resisting a specific virus, the virus must adapt to get around the block or face extinction. Now that the virus has gotten around this defense, the pressure to evolve is passed to the host species. This relationship will continue until one side “wins” or “moves on”. In evolutionary biology this is called the Red Queen Hypothesis The term is taken from the Red Queen's race in Lewis Carroll's Through the Looking-Glass. The Red Queen says, "It takes all the running you can do, to keep in the same place.” Both the virus and host have to evolve rapidly just to maintain the same relationship. This applies to many systems, but for this blog I am going to limit most of what I talk about to the retroviruses, specifically viruses like HIV and its brothers and sisters in the primate world the simian immunodeficiency viruses SIVs. Study of SIVs in their native hosts and those that successfully crossed-species to give rise to the global HIV pandemic and our HIV models in macaques have revealed the presence of a subset of genes termed host restriction factors. In the coming days (who am I kidding, at the rate I blog weeks) I am going highlight the major anti-retroviral host restriction factors and their interesting evolutionary insights. You can expect to see posts on my personal favorites Trim5a and TrimCyp along with others like Tetherin/BST2, the APOBEC family.

To me this is exactly what tracing resistance means. My work is focused at studying how restriction factors work and how they evolved.

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