Mwimanzi, F;
Ngare, I;
Toyoda, M;
Mori, M;
Mann, J;
Ndung'u, T;
Goulder, P;
(2020)
An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles.
AIDS
, 34
(9)
pp. 1325-1330.
10.1097/QAD.0000000000002559.
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Abstract
Objectives: Certain human leucocyte antigen (HLA)-B alleles (protective alleles) associate with durable immune control of HIV-1, but with substantial heterogeneity in the level of control. It remains elusive whether viral factors including Nef-mediated immune evasion function diminish protective allele effect on viral control. / Design: The naturally occurring non-Ser variant at position 9 of HIV-1 subtype C Nef has recently exhibited an association with enhanced HLA-B downregulation function and decreased susceptibility to recognition by CD8+ T cells. We therefore hypothesized this Nef genotype leads to diminished immune control mediated by protective HLA alleles. / Methods: Nef sequences were isolated from HIV-1 subtype C-infected patients harboring protective alleles and several Nef functions including downregulation of HLA-A, HLA-B, CD4, and SERINC5 were examined. Association between Nef non-Ser9 and plasma viral load was examined in two independent South African and Botswanan treatment-naïve cohorts. / Results: Nef clones isolated from protective allele+ individuals encoding Nef non-Ser9 variant exhibited greater ability to downregulate HLA-B when compared with the Ser9 variant, while other Nef functions including HLA-A, CD4, and SERINC5 downregulation activity were unaltered. By analyzing a cohort of South African participants chronically infected with subtype C HIV-1, Nef non-Ser9 associated with higher plasma viral load in patients harboring protective alleles. Corroboratively, the Nef non-Ser9 correlated with higher plasma viral load in an independent cohort in Botswana. / Conclusion: Taken together, our study identifies the Nef genotype, non-Ser9 that subverts host immune control in HIV-1 subtype C infection.
| Type: | Article |
|---|---|
| Title: | An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/QAD.0000000000002559 |
| Publisher version: | https://doi.org/10.1097/QAD.0000000000002559 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices 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.ucl.ac.uk/id/eprint/10124262 |
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