Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS.
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 gen...
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Public Library of Science (PLoS)
2007-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030088&type=printable |
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| author | Ping An Li Hua Wang Holli Hutcheson-Dilks George Nelson Sharyne Donfield James J Goedert Charles R Rinaldo Susan Buchbinder Gregory D Kirk Stephen J O'Brien Cheryl A Winkler |
| author_facet | Ping An Li Hua Wang Holli Hutcheson-Dilks George Nelson Sharyne Donfield James J Goedert Charles R Rinaldo Susan Buchbinder Gregory D Kirk Stephen J O'Brien Cheryl A Winkler |
| author_sort | Ping An |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-37e893c7987c43c18aab5f56116df98f |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2007-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-37e893c7987c43c18aab5f56116df98f2025-08-20T02:00:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-06-0136e8810.1371/journal.ppat.0030088Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS.Ping AnLi Hua WangHolli Hutcheson-DilksGeorge NelsonSharyne DonfieldJames J GoedertCharles R RinaldoSusan BuchbinderGregory D KirkStephen J O'BrienCheryl A WinklerHuman 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030088&type=printable |
| spellingShingle | Ping An Li Hua Wang Holli Hutcheson-Dilks George Nelson Sharyne Donfield James J Goedert Charles R Rinaldo Susan Buchbinder Gregory D Kirk Stephen J O'Brien Cheryl A Winkler Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. PLoS Pathogens |
| title | Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. |
| title_full | Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. |
| title_fullStr | Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. |
| title_full_unstemmed | Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. |
| title_short | Regulatory polymorphisms in the cyclophilin A gene, PPIA, accelerate progression to AIDS. |
| title_sort | regulatory polymorphisms in the cyclophilin a gene ppia accelerate progression to aids |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030088&type=printable |
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