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Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses

Luthuli, Bonisile; Gounder, Kamini; Deymier, Martin J; Dong, Krista L; Balazs, Alejandro B; Mann, Jaclyn K; Ndung'u, Thumbi; (2023) Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses. Virology , 583 pp. 14-26. 10.1016/j.virol.2023.04.001. Green open access

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Abstract

The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. Our findings suggest MTF transmission may select viruses with compact envelopes.

Type: Article
Title: Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.virol.2023.04.001
Publisher version: https://doi.org/10.1016/j.virol.2023.04.001
Language: English
Additional information: © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: HIV-1, Subtype C, Transmitted/founder, Infectious molecular clones
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10168665
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