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Research Profiles : Using trees to uproot HIV :

Variation vs. vaccine

In the virology community, HIV is infamous for its variability. As Satish put it, "Two strains of HIV can be almost 50% different. So, in a 10,000 nucleotide virus, 4000 nucleotides could be totally different, and the virus still works — which is nuts!" Since vaccines work by prepping the immune system to attack invaders that carry particular proteins, and since HIV's protein-coding genes are so variable, it is an enormous challenge to design an effective vaccine against HIV. How can one vaccine defend the body against all those different strains of the virus? Satish and other HIV researchers think that the pattern of diversification of HIV within the body might hold the key to answering this question.

HIV diversity

Circulating Diversity. This evolutionary tree shows the global diversity of HIV, as well as the diversity in the Democratic Republic of the Congo (DRC), where HIV is believed to have first gained a foothold in humans. Colors represent the different viral subtypes circulating in different parts of the world (e.g., B strains sampled from North America or Europe); black lines depict strains from the DRC.

Because the most common source of new HIV infections is unprotected sex with men, Satish reasoned that "if we actually want to stop this epidemic, the best place to attack the virus is in the semen." He and his colleagues at UC San Diego and the Veterans Administration1 knew that, as HIV invades some tissues, it becomes isolated from HIV strains in the rest of the body — a process that parallels the splitting of lineages. They reasoned that, if HIV in the male genital tract forms a distinct lineage, it might allow the genital strain to accumulate unique mutations. Furthermore, from a viral perspective, the genital tract might represent a habitat with commonalities across individuals and so could foster the evolution of convergent genetic features. Could it be that, through natural selection, HIV strains in different people evolve genetic similarities in the genital tissue? If so, perhaps a vaccine could focus not on the breadth of variation in the global population of the virus, but on specific convergent features of genital HIV strains …

1 Pillai, S.K., B. Good, S.K. Pond, J.K. Wong, M.C. Strain, D.D. Richman, and D.M. Smith. 2005. Semen-specific genetic characteristics of Human Immunodeficiency Virus Type 1 env. Journal of Virology 79:1734-1742.

HIV diversity graphic courtesy of Andrew Rambaut, University of Edinburgh

Uprooting HIV
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