ID: 170. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Stacey, Maria A.; Clare, Simon; Marsden, Morgan; Clement, Mathew; Fielding, Ceri A.; Johnson, Zoë; Ferlin, Walter; Jones, Simon A.; Kellam, Paul; Humphreys, Ian R.
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 96
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.184
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">The antiviral restriction factor interferon-induced transmembrane protein 3 (IFITM3) inhibits endocytosis-dependent entry of numerous viruses and determines susceptible to viral disease in humans. Using the murine cytomegalovirus (MCMV) model, we discovered that regulation of pro-inflammatory cytokine production is a critical function of IFITM3. IFITM3 prevented MCMV-induced weight loss and death without directly restricting MCMV replication. Instead, susceptibility of IFITM3−/− mice was attributed to an enhanced MCMV-induced lymphopenia, activation-induced NK cell death and impaired T cell responses, resulting in uncontrolled virus replication. Exacerbated pathology in IFITM3−/− mice was associated with increased expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and IFITM3 exerted cell-intrinsic inhibition of MCMV-induced IL-6 expression by myeloid cells. Although IL-6 is required for the generation of antiviral adaptive immunity, inhibiting anti-IL-6R reversed MCMV-induced pathology and control of early MCMV replication. These data suggest that IFITM3 restricts viral pathogenesis, at least in part, via regulation of pro-inflammatory cytokine production.</p> </sec> </abstract>