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p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals

Some individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that...

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Autores principales: Herbeck, Joshua, Ghorai, Suvankar, Chen, Lennie, Rinaldo, Charles R., Margolick, Joseph B., Detels, Roger, Jacobson, Lisa, Wolinsky, Steven, Mullins, James I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352077/
https://www.ncbi.nlm.nih.gov/pubmed/25746435
http://dx.doi.org/10.1371/journal.pone.0119218
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author Herbeck, Joshua
Ghorai, Suvankar
Chen, Lennie
Rinaldo, Charles R.
Margolick, Joseph B.
Detels, Roger
Jacobson, Lisa
Wolinsky, Steven
Mullins, James I.
author_facet Herbeck, Joshua
Ghorai, Suvankar
Chen, Lennie
Rinaldo, Charles R.
Margolick, Joseph B.
Detels, Roger
Jacobson, Lisa
Wolinsky, Steven
Mullins, James I.
author_sort Herbeck, Joshua
collection PubMed
description Some individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that human p21(WAF1/CIP1) (a cyclin-dependent kinase inhibitor) could play a role in resistance to HIV-1 infection in HESN, as p21 expression has been associated with suppression of HIV-1 in elite controllers and reported to block HIV-1 integration in cell culture. We measured p21 RNA expression in PBMC from 40 HESN and 40 low exposure HIV-1 seroconverters (LESC) prior to their infection using a real-time PCR assay. Comparing the 20 HESN with the highest exposure risk (median = 111 partners/2.5 years prior to the 20 LESC with the lowest exposure risk (median = 1 partner/2.5 years prior), p21 expression trended higher in HESN in only one of two experiments (P = 0.11 vs. P = 0.80). Additionally, comparison of p21 expression in the top 40 HESN (median = 73 partners/year) and lowest 40 LESC (median = 2 partners/year) showed no difference between the groups (P = 0.84). There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression (R(2) = 0.02, P = 0.12), but again only in one experiment. Hence, if p21 expression contributes to the resistance to viral infection in HESN, it likely plays a minor role evident only in those with extremely high levels of exposure to HIV-1.
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spelling pubmed-43520772015-03-17 p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals Herbeck, Joshua Ghorai, Suvankar Chen, Lennie Rinaldo, Charles R. Margolick, Joseph B. Detels, Roger Jacobson, Lisa Wolinsky, Steven Mullins, James I. PLoS One Research Article Some individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that human p21(WAF1/CIP1) (a cyclin-dependent kinase inhibitor) could play a role in resistance to HIV-1 infection in HESN, as p21 expression has been associated with suppression of HIV-1 in elite controllers and reported to block HIV-1 integration in cell culture. We measured p21 RNA expression in PBMC from 40 HESN and 40 low exposure HIV-1 seroconverters (LESC) prior to their infection using a real-time PCR assay. Comparing the 20 HESN with the highest exposure risk (median = 111 partners/2.5 years prior to the 20 LESC with the lowest exposure risk (median = 1 partner/2.5 years prior), p21 expression trended higher in HESN in only one of two experiments (P = 0.11 vs. P = 0.80). Additionally, comparison of p21 expression in the top 40 HESN (median = 73 partners/year) and lowest 40 LESC (median = 2 partners/year) showed no difference between the groups (P = 0.84). There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression (R(2) = 0.02, P = 0.12), but again only in one experiment. Hence, if p21 expression contributes to the resistance to viral infection in HESN, it likely plays a minor role evident only in those with extremely high levels of exposure to HIV-1. Public Library of Science 2015-03-06 /pmc/articles/PMC4352077/ /pubmed/25746435 http://dx.doi.org/10.1371/journal.pone.0119218 Text en © 2015 Herbeck 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
Herbeck, Joshua
Ghorai, Suvankar
Chen, Lennie
Rinaldo, Charles R.
Margolick, Joseph B.
Detels, Roger
Jacobson, Lisa
Wolinsky, Steven
Mullins, James I.
p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals
title p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals
title_full p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals
title_fullStr p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals
title_full_unstemmed p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals
title_short p21(WAF1/CIP1) RNA Expression in Highly HIV-1 Exposed, Uninfected Individuals
title_sort p21(waf1/cip1) rna expression in highly hiv-1 exposed, uninfected individuals
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352077/
https://www.ncbi.nlm.nih.gov/pubmed/25746435
http://dx.doi.org/10.1371/journal.pone.0119218
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