title: Host Responses and Regulation by NFκB Signaling in the Liver and Liver Epithelial Cells Infected with A Novel Tick-borne Bunyavirus.
abstract: Infection in humans by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus transmitted by ticks, is often associated with pronounced liver damage, especially in fatal cases. Little has been known, however, about how liver cells respond to SFTSV and how the response is regulated. In this study we report that proinflammatory cytokines were induced in liver tissues of C57/BL6 mice infected with SFTSV, which may cause tissue necrosis in mice. Human liver epithelial cells were susceptible to SFTSV and antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. We observed that infection of liver epithelial cells led to significant increases in proinflammatory cytokines and chemokines, including IL-6, RANTES, IP-10, and MIP-3a, which were regulated by NFκB signaling, and the activation of NFκB signaling during infection promoted viral replication in liver epithelial cells. Viral nonstructural protein NSs was inhibitory to the induction of IFN-β, but interestingly, NFκB activation was enhanced in the presence of NSs. Therefore, NSs plays dual roles in the suppression of antiviral IFN-β induction as well as the promotion of proinflammatory responses. Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Sun
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Jin
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhu
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, Saint Paul, MN, USA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Cardona
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Li
authors.affiliation: 1] The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Nanjing University, Nanjing, China [2] Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Twin Cities, Saint Paul, MN, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000818:Animals; D002044:Bunyaviridae Infections / Q000235:genetics* / Q000635:transmission / Q000821:virology; D054418:Chemokine CCL20 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism / Q000821:virology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D016851:Orthobunyavirus / Q000235:genetics* / Q000472:pathogenicity; D017282:Tick-Borne Diseases / Q000235:genetics* / Q000821:virology
chemical_list: C503460:Ccl5 protein, mouse; D054418:Chemokine CCL20; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B