title: Virulent and attenuated strains of duck hepatitis A virus elicit discordant innate immune responses in vivo.
abstract: Previous studies of duck hepatitis A virus infection have focused only on the pathogenicity and host response of one strain. Here, we show that the virulent SH strain and the attenuated FC64 strain induced varied pathogenicity, apoptosis and immune responses in the livers of 1-day-old ducklings. SH infection caused apoptosis and visible lesions in the liver; serum aspartate aminotransferase, alanine transaminase, alkaline phosphatase, γ-glutamyltransferase and total bilirubin activities were markedly upregulated; and ducklings died at 36 h post-infection (p.i.). However, FC64 infection did not induce significant symptoms or impair liver function, and all of the infected ducklings remained healthy. In addition, both virus strains replicated well in the liver, spleen and intestine, whilst the SH strain replicated more efficiently than FC64. IFN-γ, IL-2, inducible nitric oxide synthase and nitric oxide were strongly induced by SH infection, and may be associated with the pathogenicity of the SH strain. IFN-α, IFN-β, IFN-stimulated transmembrane protein 1, IFN-stimulated gene 12, 2',5'-oligoadenylate synthetase-like and IL-6 were moderately induced by SH infection at 24 h p.i., and dramatically induced by FC64 infection at 36 h p.i. The intensive induction of cytokines by FC64 may be involved in restriction of virus replication and stimulation of adaptive immune responses. Ducklings inoculated with FC64 produced high levels of antiviral antibodies within 45 days p.i. The low virulence and strong immune response of FC64 rendered this strain a good vaccine candidate, as confirmed by a protective assay in this study.
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Song
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Yangzhou University, College of Veterinary Medicine, 88 South University Avenue, Yangzhou 225009, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Shengqing
authors.initials: S
authors.lastname: Yu
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Xvsheng
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, 46 Xinkang Road, Ya'an 625014, PR China.
authors.forename: Anchun
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, 46 Xinkang Road, Ya'an 625014, PR China.
authors.forename: Mingshu
authors.initials: M
authors.lastname: Wang
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, PR China.
authors.forename: Chan
authors.initials: C
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis; D004372:Ducks; D004371:Hepatitis Virus, Duck / Q000276:immunology / Q000472:pathogenicity*; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D007113:Immunity, Innate; D008099:Liver / Q000473:pathology / Q000821:virology; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010850:Picornaviridae Infections / Q000662:veterinary* / Q000821:virology; D011201:Poultry Diseases / Q000276:immunology / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D014774:Virulence; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II