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Polymorphisms in the regulatory region of the Cyclophilin A gene influence the susceptibility for HIV-1 infection.

Rits MA, van Dort KA, Kootstra NA - PLoS ONE (2008)

Bottom Line: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA.The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM.Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU).

Methodology/principal findings: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

Conclusion/significance: The results obtained in this study suggest that the A1650G polymorphism in the regulatory region of the CypA gene may be associated with protection from HIV-1 infection, while the 1604G allele may have a weak association with the clinical course of infection in DU.

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Analysis of HIV-1 replication in genotyped PBMC.Replication of NL4-3 Ba-L in PHA stimulated PBMC from healthy donors homozygous for the 1604 and 1650 major allele (1604CC/1650AA), heterozygous for the 1604 minor allele (1604CG), or heterozygous for the 1650 minor allele (1650AG). Virus replication was analyzed by measuring p24 production in culture supernatant. P24 production at day 12 after infection is shown.
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pone-0003975-g003: Analysis of HIV-1 replication in genotyped PBMC.Replication of NL4-3 Ba-L in PHA stimulated PBMC from healthy donors homozygous for the 1604 and 1650 major allele (1604CC/1650AA), heterozygous for the 1604 minor allele (1604CG), or heterozygous for the 1650 minor allele (1650AG). Virus replication was analyzed by measuring p24 production in culture supernatant. P24 production at day 12 after infection is shown.

Mentions: Next, we analyzed the replicative capacity of HIV-1 in PHA-stimulated PBMC from healthy individuals with known genotypes for the C1604G and A1650G polymorphism. PHA-stimulated PBMC were inoculated with NL4-3 Ba-L (2×103 TCID50 per 5×106 cells). Subsequently, virus replication was assessed by measuring p24 antigen levels in the culture supernatant every other day for a period of two weeks. No significant differences in p24 production were observed at any time point during the culture period, irrespective of the genotype of the regulatory region of the CypA gene (figure 3).


Polymorphisms in the regulatory region of the Cyclophilin A gene influence the susceptibility for HIV-1 infection.

Rits MA, van Dort KA, Kootstra NA - PLoS ONE (2008)

Analysis of HIV-1 replication in genotyped PBMC.Replication of NL4-3 Ba-L in PHA stimulated PBMC from healthy donors homozygous for the 1604 and 1650 major allele (1604CC/1650AA), heterozygous for the 1604 minor allele (1604CG), or heterozygous for the 1650 minor allele (1650AG). Virus replication was analyzed by measuring p24 production in culture supernatant. P24 production at day 12 after infection is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2599883&req=5

pone-0003975-g003: Analysis of HIV-1 replication in genotyped PBMC.Replication of NL4-3 Ba-L in PHA stimulated PBMC from healthy donors homozygous for the 1604 and 1650 major allele (1604CC/1650AA), heterozygous for the 1604 minor allele (1604CG), or heterozygous for the 1650 minor allele (1650AG). Virus replication was analyzed by measuring p24 production in culture supernatant. P24 production at day 12 after infection is shown.
Mentions: Next, we analyzed the replicative capacity of HIV-1 in PHA-stimulated PBMC from healthy individuals with known genotypes for the C1604G and A1650G polymorphism. PHA-stimulated PBMC were inoculated with NL4-3 Ba-L (2×103 TCID50 per 5×106 cells). Subsequently, virus replication was assessed by measuring p24 antigen levels in the culture supernatant every other day for a period of two weeks. No significant differences in p24 production were observed at any time point during the culture period, irrespective of the genotype of the regulatory region of the CypA gene (figure 3).

Bottom Line: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA.The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM.Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU).

Methodology/principal findings: We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis.

Conclusion/significance: The results obtained in this study suggest that the A1650G polymorphism in the regulatory region of the CypA gene may be associated with protection from HIV-1 infection, while the 1604G allele may have a weak association with the clinical course of infection in DU.

Show MeSH
Related in: MedlinePlus