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P21<sup>WAF1/CIP1</sup> RNA expression in highly HIV-1 exposed, uninfected individuals

Herbeck, J and Ghorai, S and Chen, L and Rinaldo, CR and Margolick, JB and Detels, R and Jacobson, L and Wolinsky, S and Mullins, JI (2015) P21<sup>WAF1/CIP1</sup> RNA expression in highly HIV-1 exposed, uninfected individuals. PLoS ONE, 10 (3).

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Abstract

© 2015 Herbeck et al. 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 p21WAF1/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 (R2 = 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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Herbeck, J
Ghorai, S
Chen, L
Rinaldo, CRRINALDO@pitt.eduRINALDO
Margolick, JB
Detels, R
Jacobson, L
Wolinsky, S
Mullins, JI
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorGray, Clive M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 6 March 2015
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0119218
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
PubMed ID: 25746435
Date Deposited: 12 May 2015 18:10
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/24101

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