P21WAF1/CIP1 RNA expression in highly HIV-1 exposed, uninfected individuals

Joshua Herbeck, Suvankar Ghorai, Lennie Chen, Charles R. Rinaldo, Joseph B. Margolick, Roger Detels, Lisa Jacobson, Steven Wolinsky, James I. Mullins

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere0119218
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 6 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Herbeck, J., Ghorai, S., Chen, L., Rinaldo, C. R., Margolick, J. B., Detels, R., Jacobson, L., Wolinsky, S., & Mullins, J. I. (2015). P21WAF1/CIP1 RNA expression in highly HIV-1 exposed, uninfected individuals. PloS one, 10(3), [e0119218]. https://doi.org/10.1371/journal.pone.0119218