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- Title
HIV blocks Type I IFN signaling through disruption of STAT1 phosphorylation.
- Authors
Nguyen, Nam V.; Tran, James T.; Sanchez, David Jesse
- Abstract
This study investigates the modulation of Type I IFN induction of an antiviral state by HIV. IFNs, including IFN-α, 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-α-stimulated microenvironments. Our previous studies have shown that HIV proteins disrupt the induction of IFN-α by degradation of IFN-β promoter stimulator-1, an adaptor protein for the up-regulation and release of IFN-α into the local microenvironment via the retinoic acid-inducible gene 1-like receptor signaling pathway. However, IFN-α 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-α stimulation is disrupted by HIV proteins Vpu and Nef, which both reduce IFN-α induction of STAT1 phosphorylation. Thus, HIV would still be able to avoid antiviral protection induced by IFN-α 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-α-rich environments.
- Subjects
HIV infections -- Immunological aspects; STAT proteins; PHOSPHORYLATION; INTERFERONS; ANTIVIRAL agents; IMMUNOMODULATORS
- Publication
Innate Immunity, 2018, Vol 24, Issue 8, p490
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425918803674