Influence of Prothymosin‐α on HIV‐1 Target Cells

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Abstract
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 β‐chemokines, Rantes, MIP‐1α, MIP‐1β, and MDC. We previously identified that prothymosin alpha (ProTα) 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 ProTα 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‐α‐inducible genes including PKR, IRF1, and Rantes, in the absence of induction of IFN‐α. These data suggest that the anti‐HIV‐1 activity of ProTα 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.

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