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A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection
The establishment of latent infection and poorly characterized viral reservoirs in tissues represent major obstacles to a definitive cure for HIV. Non-human primate (NHP) models of HIV infection are critical to elucidate pathogenic processes and an essential tool to test novel therapeutic strategies...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700126/ https://www.ncbi.nlm.nih.gov/pubmed/31427605 http://dx.doi.org/10.1038/s41598-019-48354-3 |
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author | Frank, Ines Acharya, Arpan Routhu, Nanda K. Aravantinou, Meropi Harper, Justin L. Maldonado, Stephanie Sole Cigoli, Maria Semova, Stanka Mazel, Svetlana Paiardini, Mirko Derby, Nina Byrareddy, Siddappa N. Martinelli, Elena |
author_facet | Frank, Ines Acharya, Arpan Routhu, Nanda K. Aravantinou, Meropi Harper, Justin L. Maldonado, Stephanie Sole Cigoli, Maria Semova, Stanka Mazel, Svetlana Paiardini, Mirko Derby, Nina Byrareddy, Siddappa N. Martinelli, Elena |
author_sort | Frank, Ines |
collection | PubMed |
description | The establishment of latent infection and poorly characterized viral reservoirs in tissues represent major obstacles to a definitive cure for HIV. Non-human primate (NHP) models of HIV infection are critical to elucidate pathogenic processes and an essential tool to test novel therapeutic strategies. Thus, the availability of novel assays to measure residual viral replication and reservoirs in NHP models may increase their utility in the search for an HIV cure. We developed a tat/rev induced limiting dilution assay to measure the frequency of CD4(+) T cells that express multiply-spliced(ms)_SIV RNA in presence and absence of stimulation. We validated the assay using cell lines and cells from blood and lymph nodes of SIV infected macaques. In vitro, SIV/SHIV TILDA detects only cells expressing viral proteins. In SIV/SHIV-infected macaques, CD4(+) T cells that express msSIV/SHIV RNA (TILDA data) were detected also in the setting of very low/undetectable viremia. TILDA data were significantly higher after stimulation and correlated with plasma viral load (pVL). Interestingly, TILDA data from early cART initiation correlated with peak and AUC pVL post-cART interruption. In summary, we developed an assay that may be useful in characterizing viral reservoirs and determining the effect of HIV interventions in NHP models. |
format | Online Article Text |
id | pubmed-6700126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67001262019-08-21 A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection Frank, Ines Acharya, Arpan Routhu, Nanda K. Aravantinou, Meropi Harper, Justin L. Maldonado, Stephanie Sole Cigoli, Maria Semova, Stanka Mazel, Svetlana Paiardini, Mirko Derby, Nina Byrareddy, Siddappa N. Martinelli, Elena Sci Rep Article The establishment of latent infection and poorly characterized viral reservoirs in tissues represent major obstacles to a definitive cure for HIV. Non-human primate (NHP) models of HIV infection are critical to elucidate pathogenic processes and an essential tool to test novel therapeutic strategies. Thus, the availability of novel assays to measure residual viral replication and reservoirs in NHP models may increase their utility in the search for an HIV cure. We developed a tat/rev induced limiting dilution assay to measure the frequency of CD4(+) T cells that express multiply-spliced(ms)_SIV RNA in presence and absence of stimulation. We validated the assay using cell lines and cells from blood and lymph nodes of SIV infected macaques. In vitro, SIV/SHIV TILDA detects only cells expressing viral proteins. In SIV/SHIV-infected macaques, CD4(+) T cells that express msSIV/SHIV RNA (TILDA data) were detected also in the setting of very low/undetectable viremia. TILDA data were significantly higher after stimulation and correlated with plasma viral load (pVL). Interestingly, TILDA data from early cART initiation correlated with peak and AUC pVL post-cART interruption. In summary, we developed an assay that may be useful in characterizing viral reservoirs and determining the effect of HIV interventions in NHP models. Nature Publishing Group UK 2019-08-19 /pmc/articles/PMC6700126/ /pubmed/31427605 http://dx.doi.org/10.1038/s41598-019-48354-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Frank, Ines Acharya, Arpan Routhu, Nanda K. Aravantinou, Meropi Harper, Justin L. Maldonado, Stephanie Sole Cigoli, Maria Semova, Stanka Mazel, Svetlana Paiardini, Mirko Derby, Nina Byrareddy, Siddappa N. Martinelli, Elena A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection |
title | A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection |
title_full | A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection |
title_fullStr | A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection |
title_full_unstemmed | A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection |
title_short | A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection |
title_sort | tat/rev induced limiting dilution assay to measure viral reservoirs in non-human primate models of hiv infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700126/ https://www.ncbi.nlm.nih.gov/pubmed/31427605 http://dx.doi.org/10.1038/s41598-019-48354-3 |
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