Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline

AUTOR(ES)

Markham, Richard B.

FONTE

The National Academy of Sciences

RESUMO

Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.

Documentos Relacionados

• Association Between HIV-1 RNA Level and CD4 Cell Count Among Untreated HIV-Infected Individuals
• In vivo HIV-1 infection of CD45RA+CD4+ T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4+ T cell decline
• Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro
• Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro.
• Identificação de epitopos da protease de HIV-1 alvos de respostas de células T CD4+ em pacientes infectados pelo HIV-1