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 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.
Department of Global Health, University of Washington, Seattle, Washington, United States of America.
Joshua
J
Herbeck
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
Suvankar
S
Ghorai
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
Lennie
L
Chen
University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Charles R
CR
Rinaldo
Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Joseph B
JB
Margolick
Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America.
Roger
R
Detels
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Lisa
L
Jacobson
Department of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Steven
S
Wolinsky
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
James I
JI
Mullins
D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D015658:HIV Infections / Q000635:transmission / Q000821:virology; D018023:HIV Seronegativity; D015497:HIV-1; D006801:Humans; D012313:RNA / Q000235:genetics*; D012307:Risk Factors; D012747:Sexual Partners; D047568:Unsafe Sex
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012313:RNA