title: Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1.
abstract: The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Haaland
authors.forename: Paulina A
authors.initials: PA
authors.lastname: Hawkins
authors.forename: Jesus
authors.initials: J
authors.lastname: Salazar-Gonzalez
authors.forename: Amber
authors.initials: A
authors.lastname: Johnson
authors.forename: Amanda
authors.initials: A
authors.lastname: Tichacek
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.forename: Olivier
authors.initials: O
authors.lastname: Manigart
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Susan A
authors.initials: SA
authors.lastname: Allen
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
mesh_terms: D005260:Female; D005831:Genital Diseases, Female / Q000150:complications* / Q000821:virology; D005832:Genital Diseases, Male / Q000150:complications* / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000821:virology*; D008297:Male; D012432:Rwanda; D012725:Sexual Behavior; D015024:Zambia
chemical_list: D015699:HIV Envelope Protein gp120