Major vault protein: A virus-induced host factor against viral replication through the induction of type-I interferon

Major vault protein (MVP) is the major constituent of vaults and is involved in multidrug resistance, nucleocytoplasmic transport, and cell signaling. However, little is known about the role of MVP during viral infections. In this study, high levels of MVP were found in peripheral blood mononuclear cells, sera, and liver tissue from patients infected with hepatitis C virus (HCV) relative to healthy individuals. HCV infections resulted in elevated levels of MVP messenger RNA (mRNA) and protein expression in the hepatocyte cell lines Huh7.5.1 and Huh7. Further studies demonstrated that the nuclear factor kappa B (NF-?B) and Sp1 pathways are involved in the induction of MVP expression by HCV. Interestingly, MVP expression suppressed HCV replication and protein synthesis by way of induction of type-I interferon mRNA expression and protein secretion. Upon investigating the mechanisms behind this event, we found that MVP enhanced the expression of interferon regulatory factor 7 (IRF7), but not IRF3. Translocation of activated IRF7 and NF-?B from the cytosol to the nucleus was involved in this process. Furthermore, vesicular stomatitis virus, influenza A virus, and enterovirus 71 also induced MVP production, and MVP in turn hampered viral replication and production. Conclusion: MVP is a novel virus-induced host factor and its expression up-regulates type-I interferon production, leading to cellular antiviral responses. (HEPATOLOGY 2012;56:5766)