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Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies
Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART). We studied the turnover of SIV DNA r...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977820/ https://www.ncbi.nlm.nih.gov/pubmed/24710023 http://dx.doi.org/10.1371/journal.pone.0093330 |
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author | Reece, Jeanette C. Martyushev, Alexey Petravic, Janka Grimm, Andrew Gooneratne, Shayarana Amaresena, Thakshila De Rose, Robert Loh, Liyen Davenport, Miles P. Kent, Stephen J. |
author_facet | Reece, Jeanette C. Martyushev, Alexey Petravic, Janka Grimm, Andrew Gooneratne, Shayarana Amaresena, Thakshila De Rose, Robert Loh, Liyen Davenport, Miles P. Kent, Stephen J. |
author_sort | Reece, Jeanette C. |
collection | PubMed |
description | Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART). We studied the turnover of SIV DNA resting CD4+ T cells during active infection in a cohort of 20 SIV-infected pigtail macaques. We compared SIV sequences at two Mane-A1*084:01-restricted CTL epitopes using serial plasma RNA and resting CD4+ T cell DNA samples by pyrosequencing, and used a mathematical modeling approach to estimate SIV DNA turnover. We found SIV DNA turnover in resting CD4+ T cells was slow in animals with low chronic viral loads, consistent with the long persistence of latency seen under ART. However, in animals with high levels of chronic viral replication, turnover was high. SIV DNA half-life within resting CD4 cells correleated with viral load (p = 0.0052) at the Gag KP9 CTL epitope. At a second CTL epitope in Tat (KVA10) there was a trend towards an association of SIV DNA half-life in resting CD4 cells and viral load (p = 0.0971). Further, we found that the turnover of resting CD4+ T cell SIV DNA was higher for escape during early infection than for escape later in infection (p = 0.0084). Our results suggest viral DNA within resting CD4 T cells is more labile and may be more susceptible to reactivation/eradication treatments when there are higher levels of virus replication and during early/acute infection. |
format | Online Article Text |
id | pubmed-3977820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39778202014-04-11 Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies Reece, Jeanette C. Martyushev, Alexey Petravic, Janka Grimm, Andrew Gooneratne, Shayarana Amaresena, Thakshila De Rose, Robert Loh, Liyen Davenport, Miles P. Kent, Stephen J. PLoS One Research Article Resting CD4+ T cells are a reservoir of latent HIV-1. Understanding the turnover of HIV DNA in these cells has implications for the development of eradication strategies. Most studies of viral latency focus on viral persistence under antiretroviral therapy (ART). We studied the turnover of SIV DNA resting CD4+ T cells during active infection in a cohort of 20 SIV-infected pigtail macaques. We compared SIV sequences at two Mane-A1*084:01-restricted CTL epitopes using serial plasma RNA and resting CD4+ T cell DNA samples by pyrosequencing, and used a mathematical modeling approach to estimate SIV DNA turnover. We found SIV DNA turnover in resting CD4+ T cells was slow in animals with low chronic viral loads, consistent with the long persistence of latency seen under ART. However, in animals with high levels of chronic viral replication, turnover was high. SIV DNA half-life within resting CD4 cells correleated with viral load (p = 0.0052) at the Gag KP9 CTL epitope. At a second CTL epitope in Tat (KVA10) there was a trend towards an association of SIV DNA half-life in resting CD4 cells and viral load (p = 0.0971). Further, we found that the turnover of resting CD4+ T cell SIV DNA was higher for escape during early infection than for escape later in infection (p = 0.0084). Our results suggest viral DNA within resting CD4 T cells is more labile and may be more susceptible to reactivation/eradication treatments when there are higher levels of virus replication and during early/acute infection. Public Library of Science 2014-04-07 /pmc/articles/PMC3977820/ /pubmed/24710023 http://dx.doi.org/10.1371/journal.pone.0093330 Text en © 2014 Reece 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 Reece, Jeanette C. Martyushev, Alexey Petravic, Janka Grimm, Andrew Gooneratne, Shayarana Amaresena, Thakshila De Rose, Robert Loh, Liyen Davenport, Miles P. Kent, Stephen J. Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies |
title | Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies |
title_full | Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies |
title_fullStr | Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies |
title_full_unstemmed | Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies |
title_short | Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies |
title_sort | measuring turnover of siv dna in resting cd4+ t cells using pyrosequencing: implications for the timing of hiv eradication therapies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977820/ https://www.ncbi.nlm.nih.gov/pubmed/24710023 http://dx.doi.org/10.1371/journal.pone.0093330 |
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