Heterosexual Transmission of Subtype C HIV-1 Selects Consensus-Like Variants without Increased Replicative Capacity or Interferon-α Resistance

PLoS Pathogens

Susan A. Allen¹  Dario A. Dilernia²  Zachary Ende²  Martin J. Deymier²  Eric Hunter²  Persephone Borrow³  Angharad E. Fenton-May³  William Kilembe⁴ 

[1] Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America;Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America;Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;Zambia-Emory HIV Research Project, Lusaka, Zambia

关键词: Viral replication;    HIV-1;    Viral transmission;    infection;    Dendritic cells;    Interferons;    Sequence alignment;    Heterosexuals;    Phylogenetic analysis;   

DOI  :  10.1371/journal.ppat.1005154

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY