P21^WAF1/CIP1 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^WAF1/CIP1 RNA expression in highly HIV-1 exposed, uninfected individuals. PLoS ONE, 10 (3).

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Abstract

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:	Creators Email Pitt Username ORCID Herbeck, J Ghorai, S Chen, L Rinaldo, CR RINALDO@pitt.edu RINALDO Margolick, JB Detels, R Jacobson, L Wolinsky, S Mullins, JI
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Gray, Clive M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	11 Jun 2021 22:55
URI:	http://d-scholarship.pitt.edu/id/eprint/24101

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