Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic

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Upon HIV transmission, many –⁠ though not all –⁠ immune escape mutations selected in the previous host will revert to the consensus residue. The persistence of certain escape mutations following transmission has led to concerns that these could gradually accumulate in circulating HIV sequences over time, thereby undermining host antiviral immune potential as the epidemic progresses. As certain immune-driven mutations reduce viral fitness, their spread through the population could also have consequences for the average replication capacity and/or protein function of circulating HIV sequences. Here, we characterized HIV sequences, linked to host immunogenetic information, from patients enrolled in historic (1979–1989) and modern (2000–2011) HIV cohorts from four key cities in the North American epidemic. We reconstructed the epidemic's ancestral (founder) HIV sequence and assessed the subsequent extent to which known HIV immune escape mutations have spread in the population. Our data support the gradual spread of many -⁠ though not all -⁠ immune escape mutations in HIV sequences over time, but to an extent that is unlikely to have major immediate immunologic consequences for the North American epidemic. Notably, in vitro assessments of ancestral and patient-derived HIV sequences suggested functional implications of ongoing HIV evolution for certain viral proteins.

Vyšlo v časopise: Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004295
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004295

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