Your browser doesn't support javascript.
loading
Exploring the alternative virulence determinants PB2 S155N and PA S49Y/D347G that promote mammalian adaptation of the H9N2 avian influenza virus in mice.
Guo, Yanna; Bai, Xuebing; Liu, Zhiyuan; Liang, Bing; Zheng, Yiqing; Dankar, Samar; Ping, Jihui.
Afiliação
  • Guo Y; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Research Center of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
  • Bai X; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Research Center of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
  • Liu Z; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Research Center of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
  • Liang B; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Research Center of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
  • Zheng Y; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Research Center of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
  • Dankar S; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ONK1V 8M5, Canada.
  • Ping J; MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Research Center of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China. jihui.ping@njau.edu.cn.
Vet Res ; 54(1): 97, 2023 Oct 19.
Article em En | MEDLINE | ID: mdl-37858267
The occurrence of human infections caused by avian H9N2 influenza viruses has raised concerns regarding the potential for human epidemics and pandemics. The molecular basis of viral adaptation to a new host needs to be further studied. Here, the bases of nucleotides 627 and 701 of PB2 were changed according to the uncoverable purine-to-pyrimidine transversion to block the development of PB2 627K and 701N mutations during serial passaging in mice. The purpose of this experiment was to identify key adaptive mutations in polymerase and NP genes that were obscured by the widely known host range determinants PB2 627K and 701N. Mouse-adapted H9N2 variants were obtained via twelve serial lung-to-lung passages. Sequence analysis showed that the mouse-adapted viruses acquired several mutations within the seven gene segments (PB2, PB1, PA, NP, HA, NA, and NS). One variant isolate with the highest polymerase activity possessed three substitutions, PB2 S155N, PA S49Y and D347G, which contributed to the highly virulent and mouse-adaptative phenotype. Further studies demonstrated that these three mutations resulted in increased polymerase activity, viral transcription and replication in mammalian cells, severe interstitial pneumonia, excessive inflammatory cellular infiltration and increased growth rates in mice. Our results suggest that the substitution of these three amino acid mutations may be an alternative strategy for H9N2 avian influenza viruses to adapt to mammalian hosts. The continued surveillance of zoonotic H9N2 influenza viruses should also include these mammalian adaptation markers as part of our pandemic preparedness efforts.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Orthomyxoviridae / Vírus da Influenza A Subtipo H9N2 / Influenza Aviária Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Orthomyxoviridae / Vírus da Influenza A Subtipo H9N2 / Influenza Aviária Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article