title: The PA protein directly contributes to the virulence of H5N1 avian influenza viruses in domestic ducks.
abstract: During their circulation in nature, H5N1 avian influenza viruses (AIVs) have acquired the ability to kill their natural hosts, wild birds and ducks. The genetic determinants for this increased virulence are largely unknown. In this study, we compared two genetically similar H5N1 AIVs, A/duck/Hubei/49/05 (DK/49) and A/goose/Hubei/65/05 (GS/65), that are lethal for chickens but differ in their virulence levels in ducks. To explore the genetic basis for this difference in virulence, we generated a series of reassortants and mutants of these two viruses. The virulence of the reassortant bearing the PA gene from DK/49 in the GS/65 background increased 10(5)-fold relative to that of the GS/65 virus. Substitution of two amino acids, S224P and N383D, in PA contributed to the highly virulent phenotype. The amino acid 224P in PA increased the replication of the virus in duck embryo fibroblasts, and the amino acid 383D in PA increased the polymerase activity in duck embryo fibroblasts and delayed the accumulation of the PA and PB1 polymerase subunits in the nucleus of virus-infected cells. Our results provide strong evidence that the polymerase PA subunit is a virulence factor for H5N1 AIVs in ducks.
authors.affiliation: Harbin Veterinary Research Institute, CAAS, Harbin 150001, People's Republic of China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Song
authors.forename: Huapeng
authors.initials: H
authors.lastname: Feng
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shi
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
authors.forename: Guohua
authors.initials: G
authors.lastname: Deng
authors.forename: Yongping
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xuyong
authors.initials: X
authors.lastname: Li
authors.forename: Pengyang
authors.initials: P
authors.lastname: Zhu
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Guan
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Bu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Hualan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000829:Animals, Domestic / Q000821:virology; D002645:Chickens; D004372:Ducks; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000821:virology*; D008969:Molecular Sequence Data; D011201:Poultry Diseases / Q000821:virology*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: C061290:PA protein, influenza viruses; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase