Genome-wide transcriptional profiling reveals that HIV-1 Vpr differentially regulates interferon-stimulated genes in human monocyte-derived dendritic cells.

Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that directly link the innate and adaptive immune responses. HIV-1 infection of DCs leads to a diverse array of changes in gene expression and play a major role in dissemination of the virus into T-cells. Although HIV-1 Vpr is a pleiotropic protein involved in HIV-1 replication and pathogenesis, its exact role in APCs such as DCs remains elusive. In this study, utilizing a microarray-based systemic biology approach, we found that HIV-1 Vpr differentially regulates (fold change >2.0) more than 200 genes, primarily those involved in the immune response and innate immune response including type I interferon signaling pathway. The differential expression profiles of select genes involved in innate immune responses (interferon-stimulated genes [ISGs]), including MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, and TNFSF10, were validated by real-time quantitative PCR; the results were consistent with the microarray data. Taken together, our findings are the first to demonstrate that HIV-1 Vpr induces ISGs and activates the type I IFN signaling pathway in human DCs, and provide insights into the role of Vpr in HIV-1 pathogenesis.