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Phenotypic properties of envelope glycoproteins of transmitted HIV-1 variants from patients belonging to transmission chains

Beretta, Maximea; Moreau, Alaina; Bouvin-Pley, Mélaniea; Essat, Asmab; Goujard, Cécileb,c; Chaix, Marie-Laured,e; Hue, Stéphanef; Meyer, Laurenceb,c; Barin, Francisa,g; Braibant, Martinea on behalf of the ANRS 06 Primo Cohort

doi: 10.1097/QAD.0000000000001906
BASIC SCIENCE

Objective: Transmission of HIV-1 involves a bottleneck in which generally a single HIV-1 variant from a diverse viral population in the transmitting partner establishes infection in the new host. It is still unclear to what extent this event is driven by specific properties of the transmitted viruses or the result of a stochastic process. Our study aimed to better characterize this phenomenon and define properties shared by transmitted viruses.

Design: We compared antigenic and functional properties of envelope glycoproteins of viral variants found during primary infection in 27 patients belonging to eight transmission chains.

Methods: We generated pseudotyped viruses expressing Env variants of the viral quasispecies infecting each patient and compared their sensitivity to neutralization by eight human monoclonal broadly neutralizing antibodies (HuMoNAbs). We also compared their infectious properties by measuring their infectivity and sensitivity to various entry inhibitors.

Results: Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity, providing evidence that the transmission bottleneck is mainly nonstochastic. Transmitted viruses were CCR5-tropic, sensitive to MVC, and resistant to soluble forms of CD4+, irrespective of the cluster to which they belonged. They were also sensitive to HuMoNAbs that target V3, the CD4+-binding site, and the MPER region, suggesting that the loss of these epitopes may compromise their capacity to be transmitted.

Conclusion: Our data suggest that the transmission bottleneck is governed by selective forces. How these forces confer an advantage to the transmitted virus has yet to be determined.

aUniversité de Tours et CHRU de Tours, Inserm U1259, Tours

bUniversité Paris Sud, Université Paris Saclay, CESP Inserm U1018

cAP-HP Hôpital de Bicêtre, Le Kremlin-Bicêtre

dUniversité Paris Diderot, Inserm U941

eAP-HP, Hôpital Saint Louis, Laboratoire de Virologie, Paris, France

f Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom

gCHRU de Tours, CNR VIH, Tours, France.

Correspondence to Martine Braibant, PhD, Université de Tours et CHRU de Tours, Inserm U1259, Tours, France. E-mail: braibant@med.univ-tours.fr

Received 13 March, 2018

Revised 4 May, 2018

Accepted 14 May, 2018

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Copyright © 2018 Wolters Kluwer Health, Inc.