Selective pressures of human immunodeficiency virus type 1 (HIV-1) during pediatric infection

Abstract

Pediatric HIV-1 infection presents remarkable features that are distinct from those observed in adult infection. In vertically HIV-1-infected children, the viral load declines more slowly, and the cytotoxic T-lymphocyte response emerges late, only after the sixth month of life. This response generally tends to be narrow and less intense than that seen in adults. While the nuances of immune response at the cellular level during pediatric HIV-1 infection have been addressed, there is a lack of studies focusing on the consequences of this delayed and narrowed immune response at the population level. To better explore these features, we evaluated the selection regimen in gag, pol and env gene fragments of HIV-1 during pediatric infection. We estimated the number of nonsynonymous substitutions (d(N)) and synonymous substitutions (d(S)) codon-by-codon, using the maximum likelihood method and a modified counting method. Notably, both methods indicated a similar intensity of selection (measure by mean d(N)/d(S) ratio) between children and adults. Additionally, sites under positive selection were equally distributed along HIV genes and the location of these sites was analogous between children and adults. Therefore, the selective regimen in HIV during pediatric infection is equally broad and intense likewise the observed in adults. Unexpectedly, our phylogenetic-based analysis enabled us to identify two regions in the env gene of HIV with distinct adaptive functions. The first region, located in the vicinity of V3 loop, contains sites that might increase viral fitness within-host during antibody attack and virus-cell interaction. The second region, restricted to amino acids 334-368 of Gp160, contains sites that might increase viral fitness during interhost transmission at the population level.