Polymorphisms in the Regulatory Region of the Cyclophilin A Gene Influence the Susceptibility for HIV-1 Infection

Abstract

BackgroundPrevious 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 FindingsWe 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 104.5 copies per ml plasma was used as an endpoint in survival analysis.Conclusion/SignificanceThe 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.

Human Cytosolic Extracts Stabilize the HIV-1 Core

“…Cyclophilin A is a cytosolic protein that exhibits isoprolyl isomerase activity and interacts with the HIV-1 capsid protein (42)(43)(44)(45)(46). Cyclophilin A is believed to modulate the disassembly process of the HIV-1 core (47).…”

Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy

“…In addition, manipulation in CypA encoding site of PPIA gene makes it susceptible to HIV-1 infection (Rits et al, 2008), although wild type CypA are resistant to HIV-1 infection (Neagu et al, 2009). Mutation in the CypA binding residues (G89 or P90) of CA can't interact with CypA, thus prevent CypA incorporation into virions (Schaller et al, 2011;Shah et al, 2013).…”

Association of Polymorphisms in the Regulatory Region of the Cyclophilin a Gene (PPIA) with Gene Expression and HIV/AIDS Disease Progression

“…Although different groups have identified single nucleotide polymorphisms (SNPs) in the regulatory region of PPIA that affect HIV-1 clinical outcomes in different populations 10–12 , the data are inconsistent and populations studied bear less burden of HIV-1/AIDS compared to the situation in sub-Saharan Africa 13 . Bleiber et al .…”

“…While there was a non-significant association of rs6850G with CD4 cell depletion in African Americans, no evidence of association was observed in European Americans 10 . Contrary, rs6850G was significantly increased in HRSN of the Amsterdam Cohort Studies (ACS) compared to HIV-1 infected group suggesting that rs6850G may be associated with reduced susceptibility to HIV-1 infection in participants of the ACS 12 . An et al .…”