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Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Kouyos Roger D., Rusert Peter, Kadelka Claus, Huber Michael, Marzel Alex, Ebner Hanna, Schanz Merle, Liechti Thomas, Friedrich Nikolas, Braun Dominique L., Scherrer Alexandra U., Weber Jacqueline, Uhr Therese, Baumann Nicolas S., Leemann Christine, Kuster Herbert, Chave Jean-Philippe, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, KlimkaitThomas, BöniJürg, MetznerKarin, GünthardHuldrych, TrkolaAlexandra, the Swiss HIV Cohort,
Project The role of humoral immunity in HIV infection - Understanding broadly neutralizing antibody evolution
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Original article (peer-reviewed)

Journal Nature
Volume (Issue) 561(7723)
Page(s) 406 - 410
Title of proceedings Nature
DOI 10.1038/s41586-018-0517-0


Background 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. 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. Results All 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. Conclusions With 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.