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

Bonisile Luthuli; Kamini Gounder; Martin J Deymier; Krista L Dong; Alejandro B Balazs; Jaclyn K Mann; Thumbi Ndung'u

doi:10.1016/j.virol.2023.04.001

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

Virology. 2023 Jun:583:14-26. doi: 10.1016/j.virol.2023.04.001. Epub 2023 Apr 10.

Authors

Bonisile Luthuli¹, Kamini Gounder², Martin J Deymier³, Krista L Dong³, Alejandro B Balazs³, Jaclyn K Mann⁴, Thumbi Ndung'u⁵

Affiliations

¹ Africa Health Research Institute, Durban, South Africa.
² Africa Health Research Institute, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
³ The Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA.
⁴ HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
⁵ Africa Health Research Institute, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; The Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA; Division of Infection and Immunity, University College London, London, UK. Electronic address: thumbi.ndungu@ahri.org.

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.

Keywords: HIV-1; Infectious molecular clones; Subtype C; Transmitted/founder.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Clone Cells
Female
HIV Infections*
HIV-1*
Humans
Male
Persistent Infection

Abstract

Publication types

MeSH terms

Grants and funding