title: Effects of different polymerases of avian influenza viruses on the growth and pathogenicity of A/Puerto Rico/8/1934 (H1N1)-derived reassorted viruses.
abstract: We generated reassorted PR8 viruses containing six different combinations of avian influenza virus (AIV) polymerase genes from A/chicken/Korea/01310/2001 (H9N2) (01310) and A/chicken/Korea/KBNP-0028/2000 (H9N2) (0028) to examine the effects of the AIV polymerase genes PB1, PB2, and PA on replication efficiency in different host cells and pathogenicity in mice. The virus titers of the reassorted viruses possessing 01310 [rPR8-PB2(01310)] and 0028 [rPR8-PB2(0028)] PB2 genes were significantly higher than those of the others except the rPR8 virus in embryonated chicken eggs at 37°C, and those of avian polymerase reassorted viruses were significantly less than rPR8 in MDCK cells at 32 and 37°C. rPR8-PB2(01310), rPR8-PB2(0028), and rPR8-PA(0028) caused no body weight loss in BALB/c mice but rPR8-PA(01310), rPR8-PB1(01310), and rPR8-PB1(0028) caused mortality and significantly different body weight loss compared to those in the mock treatment. In contrast to rPR8-PB2(0028) and rPR8-PA(0028), rPR8-PB2(01310) was not isolated from infected mice, and rPR8-PB1(0028) was less pathogenic than rPR8-PB1(01310). We determined the amino acid residues that were specific to the less pathogenic polymerases. A comparison with those of pandemic 2009 H1N1, human fatal H5N1 and H7N9, and pathogenic AIVs to mice without adaptation revealed that they possessed the mammalian pathogenic constellation of polymerases. Thus, the novel polymerase genes and amino acid residues may be useful to understand the host-barrier overcome of AIVs in mice and to develop safer and efficacious vaccines.
authors.affiliation: Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Il-Hwan
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Avian Disease Division, Animal and Plant Quarantine Agency, 175 Anyangro, Manan-gu, Anyangsi, Gyeonggido 430-757, Republic of Korea.
authors.forename: Jun-Gu
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Avian Disease Division, Animal and Plant Quarantine Agency, 175 Anyangro, Manan-gu, Anyangsi, Gyeonggido 430-757, Republic of Korea.
authors.forename: Youn-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: kwonhj01@snu.ac.kr.
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea; Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: kimhong@snu.ac.kr.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D004285:Dogs; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D053127:Influenza A Virus, H9N2 Subtype / Q000201:enzymology / Q000235:genetics; D009980:Influenza A virus / Q000201:enzymology*; D005585:Influenza in Birds / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D016865:Reassortant Viruses / Q000378:metabolism; D056910:Republic of Korea; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D014764:Viral Proteins
keywords: Influenza A virus; Mouse; Pathogenicity; Polymerase gene; Reverse genetics