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Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-α (IFN-α) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-α resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential.

Original publication

DOI

10.1371/journal.ppat.1005154

Type

Journal article

Journal

PLoS Pathog

Publication Date

09/2015

Volume

11

Keywords

Antiviral Agents, Cells, Cultured, Cohort Studies, Dendritic Cells, Drug Resistance, Viral, Family Characteristics, Female, Genetic Variation, HIV Infections, HIV Seropositivity, HIV-1, Heterosexuality, Humans, Interferon-alpha, Leukocytes, Mononuclear, Male, Molecular Sequence Data, Molecular Typing, Phylogeny, Virion, Virus Internalization, Virus Replication, Zambia