1887

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Volume 94, Issue 5

Impact of antiretroviral pressure on selection of primary human immunodeficiency virus type 1 envelope sequences Free

Abstract

The initiation of drug therapy results in a reduction in the human immunodeficiency virus type 1 (HIV-1) population, which represents a potential genetic bottleneck. The effect of this drug-induced genetic bottleneck on the population dynamics of the envelope (Env) regions has been addressed in several studies. However, it is difficult to investigate the effect on the gene of the genetic bottleneck induced not only by entry inhibitors but also by non-entry inhibitors, particularly . Therefore, this study used an selection system using unique bulk primary isolates established in the laboratory to observe the effects of the antiretroviral drug-induced bottleneck on the integrase and genes. Env diversity was decreased significantly in one primary isolate [KP-1, harbouring both CXCR4 (X4)- and CCR5 (R5)-tropic variants] when passaged in the presence or absence of raltegravir (RAL) during selection. Furthermore, the RAL-selected KP-1 variant had a completely different Env sequence from that in the passage control (particularly evident in the gp120, V1/V2 and V4-loop regions), and a different number of potential -glycosylation sites. A similar pattern was also observed in other primary isolates when using different classes of drugs. This is the first study to explore the influence of anti-HIV drugs on bottlenecks in bulk primary HIV isolates with highly diverse Env sequences using selection.

  • Received:
  • Accepted:
  • Published Online:
© 2013 SGM
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2013-05-01
2024-04-30
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Impact of antiretroviral pressure on selection of primary human immunodeficiency virus type 1 envelope sequences in vitro
J. Gen. Virol. 94, 933 (2013); https://doi.org/10.1099/vir.0.047167-0
/content/journal/jgv/10.1099/vir.0.047167-0
/content/journal/jgv/10.1099/vir.0.047167-0
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