Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition
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 secon...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/78374 |
| _version_ | 1811203442924847104 |
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| author | Thandeka Nkosi Caroline Chasara Andrea O Papadopoulos Tiza L Nguni Farina Karim Mahomed-Yunus S Moosa Inbal Gazy Kondwani Jambo COMMIT-KZN-Team Willem Hanekom Alex Sigal Zaza M Ndhlovu |
| author_facet | Thandeka Nkosi Caroline Chasara Andrea O Papadopoulos Tiza L Nguni Farina Karim Mahomed-Yunus S Moosa Inbal Gazy Kondwani Jambo COMMIT-KZN-Team Willem Hanekom Alex Sigal Zaza M Ndhlovu |
| author_sort | Thandeka Nkosi |
| collection | DOAJ |
| description | 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+ 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+ and CD8+ 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+ 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. |
| first_indexed | 2024-04-12T02:55:49Z |
| format | Article |
| id | doaj.art-0fc2cdcb43f140b3817a81de56980d99 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:55:49Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0fc2cdcb43f140b3817a81de56980d992022-12-22T03:50:48ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.78374Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognitionThandeka Nkosi0Caroline Chasara1https://orcid.org/0000-0001-6860-6111Andrea O Papadopoulos2https://orcid.org/0000-0001-5317-1418Tiza L Nguni3Farina Karim4https://orcid.org/0000-0001-9698-016XMahomed-Yunus S Moosa5https://orcid.org/0000-0001-6191-4023Inbal Gazy6Kondwani Jambo7COMMIT-KZN-Team8Willem Hanekom9Alex Sigal10https://orcid.org/0000-0001-8571-2004Zaza M Ndhlovu11https://orcid.org/0000-0002-2708-3315Africa Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaHIV Pathogenesis Program, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaMalawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United KingdomAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South Africa; Division of Infection and Immunity, University College London, London, United KingdomAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South AfricaAfrica Health Research Institute, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South Africa; HIV Pathogenesis Program, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Ragon Institute of MGH, MIT and Harvard, Cambridge, United StatesIn 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+ 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+ and CD8+ 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+ 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.https://elifesciences.org/articles/78374SARS-CoV-2HIVT cell responsesSARS-CoV-2 variants |
| spellingShingle | Thandeka Nkosi Caroline Chasara Andrea O Papadopoulos Tiza L Nguni Farina Karim Mahomed-Yunus S Moosa Inbal Gazy Kondwani Jambo COMMIT-KZN-Team Willem Hanekom Alex Sigal Zaza M Ndhlovu Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition eLife SARS-CoV-2 HIV T cell responses SARS-CoV-2 variants |
| title | Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition |
| title_full | Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition |
| title_fullStr | Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition |
| title_full_unstemmed | Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition |
| title_short | Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition |
| title_sort | unsuppressed hiv infection impairs t cell responses to sars cov 2 infection and abrogates t cell cross recognition |
| topic | SARS-CoV-2 HIV T cell responses SARS-CoV-2 variants |
| url | https://elifesciences.org/articles/78374 |
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