title: [NP gene of pandemic H1N1 virus attenuates virulence of mouse-adapted human influenza virus].
abstract: The authors studied a possible role of the caspase cleavage motif located in the nucleoprotein (NP) of pandemic influenza virus H1N1 in the regulation of viral virulence properties. A reverse genetics method was used to obtain chimeric seasonal-like mouse-adapted influenza virus hvA/PE/8/34 (H1N10) carrying either the NP gene of wild type pandemic virus with incomplete caspase motif ETGC or mutated pandemic NP with natural caspase cleavage site of human type ETDG. The wild-type NP gene of the pandemic virus was found to poorly fit to the gene pattern of closely related seasonal-like hvA/PR/8/34 virus (H1N1) and did not rescue mature virus production whereas a mutated NP with human-type caspase cleavage site maintained gene fitness, giving rise to a chimeric virus. The generated chimeric virus hvA/PR/8/34 carrying the mutated pandemic NP successfully replicated in the murine lung, but was attenuated and did not reach the virulence level of seasonal-like mouse-adapted virus hvA/PR/8/34. The findings indicate that the NP caspase cleavage site plays a role in viral adaptation and viral virulence in mammals.
authors: O P
authors: OP
authors: Zhirnov
authors: V V
authors: VV
authors: Syrtsev
authors: F
authors: F
authors: Schwalm
authors: H D
authors: HD
authors: Klenk
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001717:Birds; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002642:Chick Embryo; D005814:Genes, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity / Q000502:physiology; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019590:Nucleocapsid Proteins; D017354:Point Mutation; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D050505:Mutant Proteins; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D020169:Caspases