Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs

Oberle, C. S. and Joos, B. and Rusert, P. and Campbell, N. K. and Beauparlant, D. and Kuster, H. and Weber, J. and Schenkel, C. D. and Scherrer, A. U. and Magnus, C. and Kouyos, R. and Rieder, P. and Niederost, B. and Braun, D. L. and Pavlovic, J. and Boni, J. and Yerly, S. and Klimkait, T. and Aubert, V. and Trkola, A. and Metzner, K. J. and Gunthard, H. F. and Swiss, H. I. V. Cohort Study. (2016) Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs. Retrovirology, 13 (1). p. 62.

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Official URL: https://edoc.unibas.ch/62182/

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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-alpha (IFNalpha) which suggests that resistance to IFNalpha cannot be a general driving force in T/F establishment. CONCLUSIONS: With the exception of increased IFNalpha 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Molecular Virology (Klimkait)
UniBasel Contributors:Klimkait, Thomas
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1742-4690 (Electronic) 1742-4690 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 May 2020 08:35
Deposited On:25 May 2020 08:35

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