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Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells
BACKGROUND: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only re...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mediscript Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337423/ https://www.ncbi.nlm.nih.gov/pubmed/28275460 |
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author | Yuan, Zhe Kang, Guobin Lu, Wuxun Li, Qingsheng |
author_facet | Yuan, Zhe Kang, Guobin Lu, Wuxun Li, Qingsheng |
author_sort | Yuan, Zhe |
collection | PubMed |
description | BACKGROUND: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses. METHODS: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted into NSG mice. Plasma viral load (pVL) and human CD4+ T cells were quantified every other week using qRT-PCR and flow cytometry. RESULTS: We found that NSG mice reactivated latently infected HIV-1 from VOA-positive CD4+ T cells as well as VOA-negative CD4+ T cells. Engrafted CD4+ T cells proliferated considerably in vivo, peaked prior to provirus reactivation, and lasted for up to 14 weeks. Sequence analyses revealed that reactivated proviruses in VOA-positive and VOA-negative CD4+ T cells are different. CONCLUSION: Taken together, NSG mice can support long-term engraftment of human CD4+ T cells and reactivate VOA-positive and VOA-negative proviruses. Therefore, this in vivo model has the potential to be used to study the underlying mechanisms of HIV-1 latency and reactivation. |
format | Online Article Text |
id | pubmed-5337423 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Mediscript Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-53374232017-03-08 Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells Yuan, Zhe Kang, Guobin Lu, Wuxun Li, Qingsheng J Virus Erad Original Research BACKGROUND: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses. METHODS: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted into NSG mice. Plasma viral load (pVL) and human CD4+ T cells were quantified every other week using qRT-PCR and flow cytometry. RESULTS: We found that NSG mice reactivated latently infected HIV-1 from VOA-positive CD4+ T cells as well as VOA-negative CD4+ T cells. Engrafted CD4+ T cells proliferated considerably in vivo, peaked prior to provirus reactivation, and lasted for up to 14 weeks. Sequence analyses revealed that reactivated proviruses in VOA-positive and VOA-negative CD4+ T cells are different. CONCLUSION: Taken together, NSG mice can support long-term engraftment of human CD4+ T cells and reactivate VOA-positive and VOA-negative proviruses. Therefore, this in vivo model has the potential to be used to study the underlying mechanisms of HIV-1 latency and reactivation. Mediscript Ltd 2017-01-01 /pmc/articles/PMC5337423/ /pubmed/28275460 Text en © 2017 The Authors. Journal of Virus Eradication published by Mediscript Ltd http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article published under the terms of a Creative Commons License. |
spellingShingle | Original Research Yuan, Zhe Kang, Guobin Lu, Wuxun Li, Qingsheng Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells |
title | Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells |
title_full | Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells |
title_fullStr | Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells |
title_full_unstemmed | Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells |
title_short | Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells |
title_sort | reactivation of hiv-1 proviruses in immune-compromised mice engrafted with human voa-negative cd4+ t cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337423/ https://www.ncbi.nlm.nih.gov/pubmed/28275460 |
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