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Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy
Incomplete restoration of CD4(+) T-cell counts on antiretroviral therapy (ART) is a major predictor of HIV-related morbidity and mortality. To understand the possible mechanisms behind this poor immunological response despite viral suppression, we longitudinally measured more than 50 virological and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092199/ https://www.ncbi.nlm.nih.gov/pubmed/33688002 http://dx.doi.org/10.1128/mBio.00099-21 |
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author | Scherpenisse, Mirte Kootstra, Neeltje A. Bakker, Margreet Berkhout, Ben Pasternak, Alexander O. |
author_facet | Scherpenisse, Mirte Kootstra, Neeltje A. Bakker, Margreet Berkhout, Ben Pasternak, Alexander O. |
author_sort | Scherpenisse, Mirte |
collection | PubMed |
description | Incomplete restoration of CD4(+) T-cell counts on antiretroviral therapy (ART) is a major predictor of HIV-related morbidity and mortality. To understand the possible mechanisms behind this poor immunological response despite viral suppression, we longitudinally measured more than 50 virological and immunological biomarkers in a cohort of HIV-infected individuals at several time points during the first 96 weeks of virologically suppressive ART. No baseline virological or immunological marker was predictive of the degree of immune reconstitution. However, the cell-associated HIV-1 unspliced-to-multiply-spliced (US/MS) RNA ratio at 12 weeks of ART positively correlated with markers of CD4(+) T-cell activation and apoptosis and negatively predicted both the absolute and relative CD4(+) T-cell counts at 48 and 96 weeks. A higher US/MS RNA ratio may reflect the higher frequency of productively infected cells that could exert pressure on the immune system, contributing to persistent immune activation and apoptosis and subsequently to a poor immunological response to ART. |
format | Online Article Text |
id | pubmed-8092199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80921992021-05-04 Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy Scherpenisse, Mirte Kootstra, Neeltje A. Bakker, Margreet Berkhout, Ben Pasternak, Alexander O. mBio Research Article Incomplete restoration of CD4(+) T-cell counts on antiretroviral therapy (ART) is a major predictor of HIV-related morbidity and mortality. To understand the possible mechanisms behind this poor immunological response despite viral suppression, we longitudinally measured more than 50 virological and immunological biomarkers in a cohort of HIV-infected individuals at several time points during the first 96 weeks of virologically suppressive ART. No baseline virological or immunological marker was predictive of the degree of immune reconstitution. However, the cell-associated HIV-1 unspliced-to-multiply-spliced (US/MS) RNA ratio at 12 weeks of ART positively correlated with markers of CD4(+) T-cell activation and apoptosis and negatively predicted both the absolute and relative CD4(+) T-cell counts at 48 and 96 weeks. A higher US/MS RNA ratio may reflect the higher frequency of productively infected cells that could exert pressure on the immune system, contributing to persistent immune activation and apoptosis and subsequently to a poor immunological response to ART. American Society for Microbiology 2021-03-09 /pmc/articles/PMC8092199/ /pubmed/33688002 http://dx.doi.org/10.1128/mBio.00099-21 Text en Copyright © 2021 Scherpenisse et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Scherpenisse, Mirte Kootstra, Neeltje A. Bakker, Margreet Berkhout, Ben Pasternak, Alexander O. Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy |
title | Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy |
title_full | Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy |
title_fullStr | Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy |
title_full_unstemmed | Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy |
title_short | Cell-Associated HIV-1 Unspliced-to-Multiply-Spliced RNA Ratio at 12 Weeks of ART Predicts Immune Reconstitution on Therapy |
title_sort | cell-associated hiv-1 unspliced-to-multiply-spliced rna ratio at 12 weeks of art predicts immune reconstitution on therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092199/ https://www.ncbi.nlm.nih.gov/pubmed/33688002 http://dx.doi.org/10.1128/mBio.00099-21 |
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