Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS

An, P and Li, HW and Hutcheson-Dilks, H and Nelson, G and Donfield, S and Goedert, JJ and Rinaldo, CR and Buchbinder, S and Kirk, GD and O'Brien, SJ and Winkler, CA (2007) Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. PLoS Pathogens, 3 (6). 0849 - 0857. ISSN 1553-7366

Published Version
Available under License : See the attached license file.

Download (485kB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4+ T-cell loss (relative hazard = 3.7, p = 0.003) in African Americans. Among European Americans, these alleles were also associated with a significant trend to more rapid progression to AIDS in a multi-point categorical analysis (p = 0.005). Both SNPs showed differential nuclear protein-binding efficiencies in a gel shift assay. In addition, one SNP (SNP5) located in the 5′ UTR previously shown to be associated with higher ex vivo HIV-1 replication was found to be more frequent in HIV-1-positive individuals than in those highly exposed uninfected individuals. These results implicate regulatory PPIA polymorphisms as a component of genetic susceptibility to HIV-1 infection or disease progression, affirming the important role of PPIA in HIV-1 pathogenesis.


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
An, P
Li, HW
Hutcheson-Dilks, H
Nelson, G
Donfield, S
Goedert, JJ
Rinaldo, CRRINALDO@pitt.eduRINALDO
Buchbinder, S
Kirk, GD
O'Brien, SJ
Winkler, CA
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 June 2007
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 3
Number: 6
Page Range: 0849 - 0857
DOI or Unique Handle: 10.1371/journal.ppat.0030088
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
ISSN: 1553-7366
PubMed ID: 17590083
Date Deposited: 12 Jul 2012 13:12
Last Modified: 22 Jun 2021 13:56


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item