Control of HIV-1C Replication Both in Vivo and in Vitro

Abstract

In this study, we established an HIV latency model using pluripotent stem cells in vitro. We found that a HIV accessory protein nef is responsible for full-length HIV silencing in human pluripotent stem cells. This effect is mediated by host factors NMT1, NMT2, Hck, PAK2, ACOT8. We further suggested that deprivation of host factors can only partially reactivate the virus. We performed a genome-wide association study (GWAS) on Botswana treatment-naïve AIDS patients infected by HIV-1C. By applying a statistical method using functional principal component analysis to approximate the underlying trajectories of longitudinal CD4 and VL, we showed three SNPs mapped to genes of HCG22, ZBTB7C and CCNG1 are significantly associated with AIDS disease progression. Our study provided insight in HIV latency mechanisms in vitro and also suggested new mechanisms of host controlling viral replication in African genetic backgrounds. Our result is important for both understanding the pathogenesis of HIV as well as treatment prioritization for AIDS intervention.