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p21(WAF1/CIP1) RNA expression in highly HIV-1 exposed, uninfected individuals.

Herbeck J, Ghorai S, Chen L, Rinaldo CR, Margolick JB, Detels R, Jacobson L, Wolinsky S, Mullins JI - PLoS ONE (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Linear regression comparisons of p21 expression in HESN and LESC.A) Linear regression of log10-transformed p21 count (number of p21 transcripts per ng of cDNA derived from total PBMC RNA) on individual pscores (the partner score, determined by the number of self-reported different sexual partners and the proportion of those partners with whom the individual had unprotected anal-receptive intercourse in the previous 2.5 years) for the top 20 ranking HESN and LESC. Shown are initial (black) and replicate (red) experiments. All individuals were of Caucasian ancestry and none possessed the CCR5Δ32 deletion. B) Plot of linear regression of p21 expression data on individual pscores for the top 40 ranking HESN and LESC, with initial (black) and replicate (red) experiments shown.
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pone.0119218.g002: Linear regression comparisons of p21 expression in HESN and LESC.A) Linear regression of log10-transformed p21 count (number of p21 transcripts per ng of cDNA derived from total PBMC RNA) on individual pscores (the partner score, determined by the number of self-reported different sexual partners and the proportion of those partners with whom the individual had unprotected anal-receptive intercourse in the previous 2.5 years) for the top 20 ranking HESN and LESC. Shown are initial (black) and replicate (red) experiments. All individuals were of Caucasian ancestry and none possessed the CCR5Δ32 deletion. B) Plot of linear regression of p21 expression data on individual pscores for the top 40 ranking HESN and LESC, with initial (black) and replicate (red) experiments shown.

Mentions: To determine whether there was a relationship between p21 expression and pscore considered as a continuous variable, p21 expression levels from the top 40 ranking HESN and the top 40 ranking LESC were compared against individual pscores with uncorrected ordinary least squares regression. There were essentially flat and non-significant linear relationships between log10-transformed p21 expression and pscore at the individual level, for both the initial and replicate experiments (R2 = 0.015, P = 0.29, R2 = 0.004, P = 0.59, respectively) (Fig. 2A). Regression analysis of only the top 20 ranking HESN and top 20 ranking LESC also showed no significant relationship, for both the initial and replicate experiments (R2 = 0.02, P = 0.45, R2 = 0.01, P = 0.66, respectively) (Fig. 2B).


p21(WAF1/CIP1) RNA expression in highly HIV-1 exposed, uninfected individuals.

Herbeck J, Ghorai S, Chen L, Rinaldo CR, Margolick JB, Detels R, Jacobson L, Wolinsky S, Mullins JI - PLoS ONE (2015)

Linear regression comparisons of p21 expression in HESN and LESC.A) Linear regression of log10-transformed p21 count (number of p21 transcripts per ng of cDNA derived from total PBMC RNA) on individual pscores (the partner score, determined by the number of self-reported different sexual partners and the proportion of those partners with whom the individual had unprotected anal-receptive intercourse in the previous 2.5 years) for the top 20 ranking HESN and LESC. Shown are initial (black) and replicate (red) experiments. All individuals were of Caucasian ancestry and none possessed the CCR5Δ32 deletion. B) Plot of linear regression of p21 expression data on individual pscores for the top 40 ranking HESN and LESC, with initial (black) and replicate (red) experiments shown.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4352077&req=5

pone.0119218.g002: Linear regression comparisons of p21 expression in HESN and LESC.A) Linear regression of log10-transformed p21 count (number of p21 transcripts per ng of cDNA derived from total PBMC RNA) on individual pscores (the partner score, determined by the number of self-reported different sexual partners and the proportion of those partners with whom the individual had unprotected anal-receptive intercourse in the previous 2.5 years) for the top 20 ranking HESN and LESC. Shown are initial (black) and replicate (red) experiments. All individuals were of Caucasian ancestry and none possessed the CCR5Δ32 deletion. B) Plot of linear regression of p21 expression data on individual pscores for the top 40 ranking HESN and LESC, with initial (black) and replicate (red) experiments shown.
Mentions: To determine whether there was a relationship between p21 expression and pscore considered as a continuous variable, p21 expression levels from the top 40 ranking HESN and the top 40 ranking LESC were compared against individual pscores with uncorrected ordinary least squares regression. There were essentially flat and non-significant linear relationships between log10-transformed p21 expression and pscore at the individual level, for both the initial and replicate experiments (R2 = 0.015, P = 0.29, R2 = 0.004, P = 0.59, respectively) (Fig. 2A). Regression analysis of only the top 20 ranking HESN and top 20 ranking LESC also showed no significant relationship, for both the initial and replicate experiments (R2 = 0.02, P = 0.45, R2 = 0.01, P = 0.66, respectively) (Fig. 2B).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus