Influence of Prothymosin-? on HIV-1 Target Cells
The important role of CD8+ T cells in controlling HIV-1 infection through the innate as well as the adaptive immune system is well established. In addition to the major histocompatibility complex (MHC)-dependent cytotoxic activity of CD8+ T cells, they produce soluble factors that suppress HIV-1 replication in an MHC-independent manner. Several of those factors have been identified, including ?-chemokines, Rantes, MIP-1?, MIP-1?, and MDC. We previously identified that prothymosin alpha (ProT?) in the conditioned medium of HVS transformed CD8+ T cells was a potent inhibitor of HIV-1 replication following proviral integration. In this report we further characterize the anti-HIV-1 activity of ProT? by demonstrating its target-cell specificity, distinction from additional inhibitors of HIV-1 transcription in CD8+ T cell supernatants, as well as the differential regulation of host cell antiviral genes that could impact HIV-1 replication. These genes include a number of transcription factors as well IFN-?-inducible genes including PKR, IRF1, and Rantes, in the absence of induction of IFN-?. These data suggest that the anti-HIV-1 activity of ProT? is mediated through the modulation of a number of genes that have been reported to suppress HIV-1 replication including the dysregulation of transcription factors and the induction of PKR and Rantes mRNA
hiv-1 prothymosin alpha irf1 macrophages dendritic cells stat2 cebp alpha runx3 ifn