Human Cytomegalovirus Inhibits IFN-α-Stimulated Antiviral and Immunoregulatory Responses by Blocking Multiple Levels of IFN-α Signal Transduction

• DOI: 10.4049/jimmunol.162.10.6107
• Publication Date: 2023-01-01T17:06:38Z
• Authors: Daniel M. Miller; Yingxue Zhang; Brian M. Rahill; W. James Waldman; Daniel D. Sedmak
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract The type I IFNs represent a primordial, tightly regulated defense system against acute viral infection. IFN-α confers resistance to infection by activating conserved signal transduction pathway that up-regulates direct antiviral effectors and induces immunomodulatory activities. Given the critical role of in anti-human cytomegalovirus (HCMV) immunity profound ability HCMV escape host immune response, we hypothesized blocks IFN-α-stimulated responses disrupting multiple levels pathway. We demonstrate inhibits MHC class I, IFN regulatory factor-1, MxA 2′,5-oligoadenylate synthetase gene expression, transcription factor activation, signaling infected fibroblasts endothelial cells decreasing expression Janus kinase 1 p48, two essential components This investigation is first report inhibition herpesvirus. propose this novel mechanism major means which capable escaping establishing persistence.