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.
Highlights
35 million people across the globe are infected with the human immunodeficiency virus type 1 (HIV-1) and an additional 2.5 million new infections occur annually [1]
In this study of populations from Zambia and Rwanda that are infected by two distinct viral genetic subtypes, we compared viral sequences that encode the entry-mediating envelope glycoproteins from newly infected individuals and their spouses very early after infection, as well as newly infected individuals infected by someone other than their spouse
In spite of the genetically diverse virus population in the donor, approximately 90% of newly infected individuals were infected by a single viral variant, while the rest were infected by multiple viral variants
Summary
35 million people across the globe are infected with the human immunodeficiency virus type 1 (HIV-1) and an additional 2.5 million new infections occur annually [1]. Almost 25 million individuals in subSaharan Africa have been infected with non-subtype B viruses via heterosexual transmission, leading to a significant gap in our understanding of the most predominant HIV-1 variants worldwide. Characterization of viral sequences in newly infected individuals has produced mixed results. Studies of individuals newly infected with subtype B have demonstrated a relatively homogenous viral population, suggesting infection by a single variant [2,3,4]. Studies involving subtype-B virus transmission in a population harboring sexually-transmitted diseases and subtype-A virus in a sex-worker cohort suggest multiple viral variants can be transmitted and are capable of establishing infection in a new host [5,6,7,8].
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