title: Interferon-inducible antiviral protein MxA enhances cell death triggered by endoplasmic reticulum stress.
abstract: Human myxovirus resistance gene A (MxA) is a type I interferon-inducible protein and exhibits the antiviral activity against a variety of RNA viruses, including influenza virus. Previously, we reported that MxA accelerates cell death of influenza virus-infected cells through caspase-dependent and -independent mechanisms. Similar to other viruses, influenza virus infection induces endoplasmic reticulum (ER) stress, which is one of cell death inducers. Here, we have demonstrated that MxA enhances ER stress signaling in cells infected with influenza virus. ER stress-induced events, such as expression of BiP mRNA and processing of XBP1 mRNA, were upregulated in cells expressing MxA by treatment with an ER stress inducer, tunicamycin (TM), as well as influenza virus infection. TM-induced cell death was also accelerated by MxA. Furthermore, we showed that MxA interacts with BiP and overexpression of BiP reduces MxA-promoted ER stress signaling. Because cell death in virus-infected cells is one of ultimate anti-virus mechanisms, we propose that MxA-enhanced ER stress signaling is a part of the antiviral activity of MxA by accelerating cell death.
authors: Department of Infection Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.
authors: Akiko
authors: A
authors: Numajiri Haruki
authors: Tadasuke
authors: T
authors: Naito
authors: Tomomi
authors: T
authors: Nishie
authors: Shoko
authors: S
authors: Saito
authors: Kyosuke
authors: K
authors: Nagata
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000302:isolation & purification; D007251:Influenza, Human / Q000276:immunology / Q000821:virology; D051379:Mice; D064547:Myxovirus Resistance Proteins; D015398:Signal Transduction; D041701:Swiss 3T3 Cells; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D014415:Tunicamycin; D019204:GTP-Binding Proteins