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A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection
Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the follo...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653877/ https://www.ncbi.nlm.nih.gov/pubmed/23691172 http://dx.doi.org/10.1371/journal.pone.0064219 |
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author | Bacchus, Charline Cheret, Antoine Avettand-Fenoël, Véronique Nembot, Georges Mélard, Adeline Blanc, Catherine Lascoux-Combe, Caroline Slama, Laurence Allegre, Thierry Allavena, Clotilde Yazdanpanah, Yazdan Duvivier, Claudine Katlama, Christine Goujard, Cécile Seksik, Bao Chau Phung Leplatois, Anne Molina, Jean-Michel Meyer, Laurence Autran, Brigitte Rouzioux, Christine |
author_facet | Bacchus, Charline Cheret, Antoine Avettand-Fenoël, Véronique Nembot, Georges Mélard, Adeline Blanc, Catherine Lascoux-Combe, Caroline Slama, Laurence Allegre, Thierry Allavena, Clotilde Yazdanpanah, Yazdan Duvivier, Claudine Katlama, Christine Goujard, Cécile Seksik, Bao Chau Phung Leplatois, Anne Molina, Jean-Michel Meyer, Laurence Autran, Brigitte Rouzioux, Christine |
author_sort | Bacchus, Charline |
collection | PubMed |
description | Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3−CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that subset activation and skewed immune homeostasis determine the conditions of viral dissemination and early establishment of the HIV reservoir. |
format | Online Article Text |
id | pubmed-3653877 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36538772013-05-20 A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection Bacchus, Charline Cheret, Antoine Avettand-Fenoël, Véronique Nembot, Georges Mélard, Adeline Blanc, Catherine Lascoux-Combe, Caroline Slama, Laurence Allegre, Thierry Allavena, Clotilde Yazdanpanah, Yazdan Duvivier, Claudine Katlama, Christine Goujard, Cécile Seksik, Bao Chau Phung Leplatois, Anne Molina, Jean-Michel Meyer, Laurence Autran, Brigitte Rouzioux, Christine PLoS One Research Article Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3−CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that subset activation and skewed immune homeostasis determine the conditions of viral dissemination and early establishment of the HIV reservoir. Public Library of Science 2013-05-14 /pmc/articles/PMC3653877/ /pubmed/23691172 http://dx.doi.org/10.1371/journal.pone.0064219 Text en © 2013 Bacchus et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bacchus, Charline Cheret, Antoine Avettand-Fenoël, Véronique Nembot, Georges Mélard, Adeline Blanc, Catherine Lascoux-Combe, Caroline Slama, Laurence Allegre, Thierry Allavena, Clotilde Yazdanpanah, Yazdan Duvivier, Claudine Katlama, Christine Goujard, Cécile Seksik, Bao Chau Phung Leplatois, Anne Molina, Jean-Michel Meyer, Laurence Autran, Brigitte Rouzioux, Christine A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection |
title | A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection |
title_full | A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection |
title_fullStr | A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection |
title_full_unstemmed | A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection |
title_short | A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection |
title_sort | single hiv-1 cluster and a skewed immune homeostasis drive the early spread of hiv among resting cd4+ cell subsets within one month post-infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653877/ https://www.ncbi.nlm.nih.gov/pubmed/23691172 http://dx.doi.org/10.1371/journal.pone.0064219 |
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