Selection in context: patterns of natural selection in the glycoprotein 120 region of human immunodeficiency virus 1 within infected individuals
Abstract
Evolution of the HIV-1 V3 loop was monitored in 15 subjects over a period of 5 years at approximately 6-month intervals. Putative recombination was detected in many of the sequences. Evolutionary trees were estimated from the nonrecombinant viral sequences found in each individual. Selection and altered demographic regimes were detected with logit and other contingency analyses in a highly context-dependent fashion. Mutations leading to amino acid substitutions are subject to positive selection over a broad range of clinical conditions in the nonsyncytium-inducing (NSI) form, and the growth rates of the NSI strains and their level of genetic subdivision change little in going from a healthy immune system to a severely compromised immune system. In contrast, the SI form has a significant increase in growth rate as the immune system goes from healthy to compromised, particularly in those subjects who did not receive any antiviral drug therapy. This increase in SI growth rate results in a significant growth advantage of SI over NSI when the immune system is compromised. The SI strains also show more demographic subdivision when the immune system is healthy than when the immune system is compromised, and the SI form has greater dem...Continue Reading
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