%0 Journal Article
%T HIV blocks Type I IFN signaling through disruption of STAT1 phosphorylation
%A David Jesse Sanchez
%A James T Tran
%A Nam V Nguyen
%J Innate Immunity
%@ 1753-4267
%D 2018
%R 10.1177/1753425918803674
%X This study investigates the modulation of Type I IFN induction of an antiviral state by HIV. IFNs, including IFN-¦Á, are key innate immune cytokines that activate the JAK/STAT pathway leading to the expression of IFN-stimulated genes. IFN-stimulated gene expression establishes the antiviral state, limiting viral infection in IFN-¦Á-stimulated microenvironments. Our previous studies have shown that HIV proteins disrupt the induction of IFN-¦Á by degradation of IFN-¦Â promoter stimulator-1, an adaptor protein for the up-regulation and release of IFN-¦Á into the local microenvironment via the retinoic acid-inducible gene 1-like receptor signaling pathway. However, IFN-¦Á is still released from other sources such as plasmacytoid dendritic cells via TLR-dependent recognition of HIV. Here we report that the activation of the JAK/STAT pathway by IFN-¦Á stimulation is disrupted by HIV proteins Vpu and Nef, which both reduce IFN-¦Á induction of STAT1 phosphorylation. Thus, HIV would still be able to avoid antiviral protection induced by IFN-¦Á in the local microenvironment. These findings show that HIV blocks multiple signaling points that would lead to the up-regulation of IFN-stimulated genes, allowing more effective replication in IFN-¦Á-rich environments
%K Interferon
%K immune evasion
%K HIV
%K AIDS
%K STAT1
%U https://journals.sagepub.com/doi/full/10.1177/1753425918803674