title: Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein.
abstract: Influenza A virus (IAV) is an important pathogen that has a wide range of hosts and represents a threat to the health of humans and several animal species. IAV infection can induce the transcription of many genes in the host. In the present study, we demonstrated for the first time that three different strains of H1N1 IAV induce the expression of an IFN-stimulated gene, ISG20. We determined the antiviral activity of ISG20 against IAV because ISG20 inhibited viral protein expression and reduced the progeny viral titer dependent upon its exonuclease activity. To elucidate the detailed mechanism of ISG20, we further demonstrated that ISG20 impairs the polymerase activity and inhibits both the replication and transcription levels of the M1 and NP genes. Notably, we identified that ISG20 colocalizes and interacts with NP during IAV infection, while exonuclease-inactive mutant ISG20 lacked association with NP, indicating that ISG20 inhibits IAV replication by interacting with NP. Together, these data provide a detailed explanation for the specific antiviral action of ISG20 and suggest that ISG20 may act as a promising antiviral drug candidate against IAV.
authors.affiliation: National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
authors.forename: Hongren
authors.initials: H
authors.lastname: Qu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. liuwj@im.ac.cn.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: National Research Center for Wildlife-Borne Diseases, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China. hehx@ioz.ac.cn.
authors.forename: Hongxuan
authors.initials: H
authors.lastname: He
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005092:Exonucleases / Q000737:chemistry / Q000235:genetics*; D005095:Exoribonucleases; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human; D009154:Mutation; D009698:Nucleoproteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014779:Virus Replication
chemical_list: D009698:Nucleoproteins; D005092:Exonucleases; D005095:Exoribonucleases; C112346:ISG20 protein, human
keywords: Exonuclease; IFN-stimulated gene; Polymerase activity