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).
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Herbeck, J | | | | Ghorai, S | | | | Chen, L | | | | Rinaldo, CR | RINALDO@pitt.edu | RINALDO | | Margolick, JB | | | | Detels, R | | | | Jacobson, L | | | | Wolinsky, S | | | | Mullins, JI | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID |
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Editor | Gray, Clive M. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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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