Nkosi, Thandeka, Chasara, Caroline, Papadopoulos, Andrea O, Nguni, Tiza L, Karim, Farina, Moosa, Mahomed-Yunus S, Gazy, Inbal, Jambo, Kondwani 
ORCID: 0000-0002-3195-2210, Hanekom, Willem, Sigal, Alex et al (show 1 more authors)
(2022)
Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition.
ELIFE, 11.
e78374-.
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Abstract
In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following peripheral blood mononuclear cell stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4<sup>+</sup> T cell responses against the Spike protein compared to the viremic people living with HIV (PLWH). Absolute CD4 count correlated positively with SARS-CoV-2-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses (CD4 r=0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4<sup>+</sup> T cell responses (CD4 r=-0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Taken together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SARS-CoV-2, HIV, T cell responses, SARS-CoV-2 variants, Human |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 Apr 2023 12:21 |
| Last Modified: | 24 Apr 2023 12:21 |
| DOI: | 10.7554/eLife.78374 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169919 |
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