title: Impacts of different expressions of PA-X protein on 2009 pandemic H1N1 virus replication, pathogenicity and host immune responses.
abstract: Although several studies have investigated the functions of influenza PA-X, the impact of different expressions of PA-X protein including full-length, truncated or PA-X deficient forms on virus replication, pathogenicity and host response remains unclear. Herein, we generated two mutated viruses expressing a full-length or deficient PA-X protein based on the A/California/04/2009 (H1N1) virus that expresses a truncated PA-X to understand three different expressions of PA-X protein on virus replication, pathogenicity and host immune responses. The results showed that expression of either full-length or truncated PA-X protein enhanced viral replication and pathogenicity as well as reduced host innate immune response in mice by host shutoff activity when compared to the virus expressing the deficient PA-X form. Furthermore, the full-length PA-X expression exhibited a greater effect on virus pathogenicity than the truncated PA-X form. Our results provide novel insights of PA-X on viral replication, pathogenicity and host immune responses.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Yonghai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jingjiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Yuekun
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Duff
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Henningson
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Abdou
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Bawa
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Tong
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Richt
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA. Electronic address: wma@vet.k-state.edu.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004285:Dogs; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: C573926:PA-X protein, influenza A virus; D020033:Protein Isoforms; D012097:Repressor Proteins; D017361:Viral Nonstructural Proteins
keywords: Host immune response; Influenza A virus; PA-X; Virus replication