Abstract
BackgroundMucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. To what extent HIV-1 transmission is a stochastic process or driven by selective forces that allow T/F viruses best to overcome bottlenecks in transmission has not been conclusively resolved. Building on prior investigations that suggest HIV-1 envelope (Env) features to contribute in the selection process during transmission, we compared phenotypic virus characteristics of nine HIV-1 subtype B transmission pairs, six men who have sex with men and three male-to-female transmission pairs.ResultsAll recipients were identified early in acute infection and harbored based on extensive sequencing analysis a single T/F virus allowing a controlled analysis of virus properties in matched transmission pairs. Recipient and transmitter viruses from the closest time point to transmission showed no signs of selection for specific Env modifications such as variable loop length and glycosylation. Recipient viruses were resistant to circulating plasma antibodies of the transmitter and also showed no altered sensitivity to a large panel of entry inhibitors and neutralizing antibodies. The recipient virus did not consistently differ from the transmitter virus in terms of entry kinetics, cell–cell transmission and replicative capacity in primary cells. Our paired analysis revealed a higher sensitivity of several recipient virus isolates to interferon-α (IFNα) which suggests that resistance to IFNα cannot be a general driving force in T/F establishment.ConclusionsWith the exception of increased IFNα sensitivity, none of the phenotypic virus properties we investigated clearly distinguished T/F viruses from their matched transmitter viruses supporting the notion that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0299-0) contains supplementary material, which is available to authorized users.
Highlights
Mucosal human immunodeficiency virus type 1 (HIV-1) transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population
Based on the investigated phenotypic virus properties, our findings suggest that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic
If and which of these many phenotypic properties truly govern transmission has not been conclusively resolved as the investigated cohorts often lacked information on linked transmission partners, or cohorts differed in the transmission mode and the subtype studied
Summary
Mucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. Findings that only few viral variants are transmitted and seed a new infection were substantiated by single genome amplification (SGA) approaches which revealed that depending on the mode of sexual transmission, in 60–90 % of cases a single HIV-1 variant [termed the transmitted/founder (T/F) virus], establishes an infection [11,12,13,14,15] These findings funneled intensive research efforts aiming to understand if the limited transmission of viral variants is due to selective forces acting during transmission and early infection or is the result of a stochastic process (reviewed in [6, 7]). A study in injection drug users of HIV-1 subtype B as well as a recent publication investigating six HIV-1 subtype C transmission pairs could not reproduce higher IFNα resistance of acute viruses [26, 36]
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