MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Kenneth W WitwerJanice E Clements

Abstract

IFN-beta production is an inaugural event in the innate immune response to viral infections, with relatively small fold changes in IFN-beta expression resulting in the activation of important antiviral signaling cascades. In our rapid SIV/macaque model of HIV encephalitis, the virus enters the CNS within 4 d of infection, accompanied by a marked IFN-beta response that wanes as SIV replication is controlled. The centrality of IFN-beta to the innate antiviral response in the CNS combines with the potential inflammatory damage associated with long-term activation of this pathway to suggest that IFN-beta may be subject to regulatory fine-tuning in addition to well-established transcriptional and message stability mechanisms of regulation. In this paper, we present for the first time evidence that microRNAs (miRNAs), including miR-26a, -34a, -145, and let-7b, may directly regulate IFN-beta in human and macaque cells. In primary primate macrophages, the main cell type implicated in HIV and SIV infection in the CNS, specific miRNAs reduce, whereas miRNA inhibitors enhance, IFN-beta protein production. The potential biologic significance of this regulation is supported by evidence of an apparent negative feedback loop, with increased e...Continue Reading

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