Partial compartmentalisation of HIV-1 subtype C between lymph nodes, peripheral blood mononuclear cells and plasma

Neschika Jeewanraj; Tawanda Mandizvo; Takalani Mulaudzi; Nombali Gumede; Zaza Ndhlovu; Thumbi Ndung'u; Kamini Gounder; Jaclyn Mann

doi:10.1016/j.virol.2023.03.011

Partial compartmentalisation of HIV-1 subtype C between lymph nodes, peripheral blood mononuclear cells and plasma

Virology. 2023 May:582:62-70. doi: 10.1016/j.virol.2023.03.011. Epub 2023 Mar 30.

Authors

Neschika Jeewanraj¹, Tawanda Mandizvo², Takalani Mulaudzi¹, Nombali Gumede¹, Zaza Ndhlovu³, Thumbi Ndung'u⁴, Kamini Gounder², Jaclyn Mann⁵

Affiliations

¹ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
² HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, Durban, South Africa.
³ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
⁴ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Division of Infection and Immunity, University College London, London, United Kingdom.
⁵ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. Electronic address: mannj@ukzn.ac.za.

Abstract

HIV-1 compartmentalisation is likely to have important implications for a preventative vaccine as well as eradication strategies. We genetically characterised HIV-1 subtype C variants in lymph nodes, peripheral blood mononuclear cells and plasma of six antiretroviral (ART) naïve individuals and four individuals on ART. Full-length env (n = 171) and gag (n = 250) sequences were generated from participants using single genome amplification. Phylogenetic relatedness of sequences was assessed, and compartmentalisation was determined using both distance and tree-based methods implemented in HyPhy. Additionally, potential associations between compartmentalisation and immune escape mutations were assessed. Partial viral compartmentalisation was present in nine of the ten participants. Broadly neutralising antibody (bnAb) escape was found to be associated with partial env compartmentalisation in some individuals, while cytotoxic T lymphocyte escape mutations in Gag were limited and did not differ between compartments. Viral compartmentalisation may be an important consideration for bnAb use in viral eradication.

Keywords: Compartmentalisation; Envelope; Gag; HIV-1; Lymph node; Peripheral blood mononuclear cells; Plasma; Single genome amplification.

Publication types

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

MeSH terms

Broadly Neutralizing Antibodies
HIV Infections*
HIV-1*
Humans
Leukocytes, Mononuclear
Lymph Nodes
Phylogeny

Substances

Broadly Neutralizing Antibodies

Abstract

Publication types

MeSH terms

Substances

Grants and funding