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Paradise Madlala, PhD HIV Pathogenesis Programme (HPP) University of University of KwaZulu-Natal

Association Polymorphisms in the Regulatory Region of Cyclophilin A gene ( PPIA ) with Gene Expression Levels and HIV/AIDS Disease Progression. Paradise Madlala, PhD HIV Pathogenesis Programme (HPP) University of University of KwaZulu-Natal. Background.

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Paradise Madlala, PhD HIV Pathogenesis Programme (HPP) University of University of KwaZulu-Natal

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  1. Association Polymorphisms in the Regulatory Region of Cyclophilin A gene (PPIA) with Gene Expression Levels and HIV/AIDS Disease Progression Paradise Madlala, PhD HIV Pathogenesis Programme (HPP) University of University of KwaZulu-Natal

  2. Background • We investigated the association of two SNPs (C1604G and A1650G) with HIV-1 clinical out comes in the CAPRISA AI 002 and Sinikithemba cohorts. PRC-RFLP was used to genotype the SNPs. • Real time RT-PCR was used to quantify CypA mRNA expression levels in PBMCs genotyped for A1650G. • HIV-1 replication capacity was performed in PBMCs genotyped for A1650G

  3. Association of 1650G with faster rate of CD4+ T Cell Decline in Sinikithemba Cohort

  4. CypA expression levels and HIV-1 replication and in genotyped PBMCs

  5. Discussion and Conclusion • The minor allele (G) of SNP A1650G (1650G) was associated with lower CD4+ T cell counts and higher viral loads during primary HIV-1 infection and rapid CD4+ T cell decline during chronic infection in black South Africans. • Following HIV-1 infection, 1650G was associated with higher CypA mRNA expression levels in vivo. However, no differences were observed in HIV-1 negative participants. • IL2/PHA stimulated PBMCs genotyped for SNP A1650G also showed no differences in CypA mRNA expression prior to HIV-1 infection in vitro. • HIV-1 infection results in differential CypA mRNA expression between AA versus AG/GG individuals.

  6. Acknowledgements UKZN • Prof. Salim Karim • Prof. Bruce Walker • Prof. Philip Goulder • Prof. Thumbi Ndung’u Ravesh Singh NCI • Dr. Cheryl Winkler KU Leuven • Prof. Zeger Debyser Funding • EU FP7- THINC Consortium • DST/NRF • NIH • UKZN Dr. An Ping

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