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Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV
Latently infected CD4 lymphocytes preclude cure of HIV infection, even with the most effective antiretroviral therapy. The replication competent latent HIV reservoir has been quantified with the terminal dilution quantitative viral outgrowth assay, which induces virus propagation in CD4(+) T cell cu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377736/ https://www.ncbi.nlm.nih.gov/pubmed/30770748 http://dx.doi.org/10.1186/s12977-019-0466-1 |
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author | Richman, Douglas D. Huang, Karissa Lada, Steven M. Sun, Xiaoying Jain, Sonia Massanella, Marta Menke, Bryson |
author_facet | Richman, Douglas D. Huang, Karissa Lada, Steven M. Sun, Xiaoying Jain, Sonia Massanella, Marta Menke, Bryson |
author_sort | Richman, Douglas D. |
collection | PubMed |
description | Latently infected CD4 lymphocytes preclude cure of HIV infection, even with the most effective antiretroviral therapy. The replication competent latent HIV reservoir has been quantified with the terminal dilution quantitative viral outgrowth assay, which induces virus propagation in CD4(+) T cell culture supernatants following cellular activation. Efforts to improve the sensitivity of this inefficient assay have introduced more sensitive p24 ELISA and RNA PCR based endpoints, but these more sensitive endpoints have raised the question whether they are measuring induced replication competent or defective virions. Here we performed parallel terminal dilution assays with CD4 lymphocytes from subjects effectively treated with antiretroviral therapy. An HIV integrase inhibitor was incorporated into one set of parallel cultures to compare the frequency of cells that can be induced to produce virions to those that produce virus that can propagate and amplify with co-culture in permissive cells. The majority of cells that can be induced to generate virus particles are producing replication competent virus, thus justifying more sensitive and faster assays of this reservoir. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-019-0466-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6377736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63777362019-02-27 Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV Richman, Douglas D. Huang, Karissa Lada, Steven M. Sun, Xiaoying Jain, Sonia Massanella, Marta Menke, Bryson Retrovirology Short Report Latently infected CD4 lymphocytes preclude cure of HIV infection, even with the most effective antiretroviral therapy. The replication competent latent HIV reservoir has been quantified with the terminal dilution quantitative viral outgrowth assay, which induces virus propagation in CD4(+) T cell culture supernatants following cellular activation. Efforts to improve the sensitivity of this inefficient assay have introduced more sensitive p24 ELISA and RNA PCR based endpoints, but these more sensitive endpoints have raised the question whether they are measuring induced replication competent or defective virions. Here we performed parallel terminal dilution assays with CD4 lymphocytes from subjects effectively treated with antiretroviral therapy. An HIV integrase inhibitor was incorporated into one set of parallel cultures to compare the frequency of cells that can be induced to produce virions to those that produce virus that can propagate and amplify with co-culture in permissive cells. The majority of cells that can be induced to generate virus particles are producing replication competent virus, thus justifying more sensitive and faster assays of this reservoir. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12977-019-0466-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-15 /pmc/articles/PMC6377736/ /pubmed/30770748 http://dx.doi.org/10.1186/s12977-019-0466-1 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Short Report Richman, Douglas D. Huang, Karissa Lada, Steven M. Sun, Xiaoying Jain, Sonia Massanella, Marta Menke, Bryson Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV |
title | Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV |
title_full | Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV |
title_fullStr | Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV |
title_full_unstemmed | Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV |
title_short | Replication competence of virions induced from CD4+ lymphocytes latently infected with HIV |
title_sort | replication competence of virions induced from cd4+ lymphocytes latently infected with hiv |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377736/ https://www.ncbi.nlm.nih.gov/pubmed/30770748 http://dx.doi.org/10.1186/s12977-019-0466-1 |
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