HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS
Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infe...
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| Format: | Article |
| Language: | English |
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Case Western Reserve University
2024-02-01
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| Series: | Pathogens and Immunity |
| Subjects: | |
| Online Access: | https://www.paijournal.com/index.php/paijournal/article/view/638 |
| _version_ | 1797296773396430848 |
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| author | Clayton Faua Axel Ursenbach Anne Fuchs Stéphanie Caspar Frédéric Jegou Yvon Ruch Baptiste Hoellinger Elodie Laugel Aurélie Velay David Rey Samira Fafi-Kremer Pierre Gantner |
| author_facet | Clayton Faua Axel Ursenbach Anne Fuchs Stéphanie Caspar Frédéric Jegou Yvon Ruch Baptiste Hoellinger Elodie Laugel Aurélie Velay David Rey Samira Fafi-Kremer Pierre Gantner |
| author_sort | Clayton Faua |
| collection | DOAJ |
| description |
Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage.
Methods: Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively.
Results: The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4low, HLA-ABClow, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, TTD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1.
Conclusions: In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection.
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| first_indexed | 2024-03-07T22:10:38Z |
| format | Article |
| id | doaj.art-ead386184e6940d585c10e1297ad700d |
| institution | Directory Open Access Journal |
| issn | 2469-2964 |
| language | English |
| last_indexed | 2024-03-07T22:10:38Z |
| publishDate | 2024-02-01 |
| publisher | Case Western Reserve University |
| record_format | Article |
| series | Pathogens and Immunity |
| spelling | doaj.art-ead386184e6940d585c10e1297ad700d2024-02-23T16:05:32ZengCase Western Reserve UniversityPathogens and Immunity2469-29642024-02-018210.20411/pai.v8i2.638HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDSClayton Faua0Axel Ursenbach1Anne Fuchs2Stéphanie Caspar3Frédéric Jegou4Yvon Ruch5Baptiste Hoellinger6Elodie Laugel7Aurélie Velay8David Rey9Samira Fafi-Kremer10Pierre Gantner11INSERM UMR_S1109, Strasbourg University, Strasbourg, FranceLe Trait d’Union, HIV-Infection Care Center, Strasbourg University Hospital, Strasbourg, FranceClinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, FranceClinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, FranceClinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, FranceInfectious Diseases Department, Strasbourg University Hospital, Strasbourg, FranceInfectious Diseases Department, Strasbourg University Hospital, Strasbourg, FranceINSERM UMR_S1109, Strasbourg University; Clinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, FranceINSERM UMR_S1109, Strasbourg University; Clinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, FranceLe Trait d’Union, HIV-Infection Care Center, Strasbourg University Hospital, Strasbourg, FranceINSERM UMR_S1109, Strasbourg University; Clinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, FranceINSERM UMR_S1109, Strasbourg University; Clinical Virology Laboratory, Strasbourg University Hospital, Strasbourg, France Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage. Methods: Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively. Results: The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4low, HLA-ABClow, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, TTD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1. Conclusions: In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection. https://www.paijournal.com/index.php/paijournal/article/view/638AIDSrecent infectionproductively infected cellsphenotypeexhaustion |
| spellingShingle | Clayton Faua Axel Ursenbach Anne Fuchs Stéphanie Caspar Frédéric Jegou Yvon Ruch Baptiste Hoellinger Elodie Laugel Aurélie Velay David Rey Samira Fafi-Kremer Pierre Gantner HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS Pathogens and Immunity AIDS recent infection productively infected cells phenotype exhaustion |
| title | HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS |
| title_full | HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS |
| title_fullStr | HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS |
| title_full_unstemmed | HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS |
| title_short | HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS |
| title_sort | hiv productively infects highly differentiated and exhausted cd4 t cells during aids |
| topic | AIDS recent infection productively infected cells phenotype exhaustion |
| url | https://www.paijournal.com/index.php/paijournal/article/view/638 |
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