Primary macrophages rely on histone deacetylase 1 and 2 expression to induce type I interferon in response to gammaherpesvirus infection

Journal of Virology
Bryan C MounceVera L Tarakanova

Abstract

Type I interferon is induced shortly following viral infection and represents a first line of host defense against a majority of viral pathogens. Not surprisingly, both replication and latency of gammaherpesviruses, ubiquitous cancer-associated pathogens, are attenuated by type I interferon, although the mechanism of attenuation remains poorly characterized. Gammaherpesviruses also target histone deacetylases (HDACs), a family of pleiotropic enzymes that modify gene expression and several cell signaling pathways. Specifically, we have previously shown that a conserved gammaherpesvirus protein kinase interacts with HDAC1 and -2 to promote gammaherpesvirus replication in primary macrophages. In the current study, we have used genetic approaches to show that expression of HDAC1 and -2 is critical for induction of a type I interferon response following gammaherpesvirus infection of primary macrophages. Specifically, expression of HDAC1 and -2 was required for phosphorylation of interferon regulatory factor 3 (IRF3) and accumulation of IRF3 at the beta interferon promoter in gammaherpesvirus-infected primary macrophages. To our knowledge, this is the first demonstration of a specific role for HDAC1 and -2 in the induction of type I ...Continue Reading

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Citations

Oct 30, 2016·Antioxidants & Redox Signaling·Marten A Hoeksema, Menno P de Winther
May 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yongxu LuGeoffrey L Smith

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