title: Mutations in the C-terminal tail of NS1 protein facilitate the replication of classical swine H1N1 influenza A virus in mice.
abstract: The NS1 protein of classical swine H1N1 influenza A virus evolved dynamically during the past 80 years, most notable changes happened in the four C-terminal sequences and the C-terminal truncation of 11 amino acids. However, the role of these changes on the virulence of classical swine H1N1 influenza A virus remains unknown. Using reverse genetics, three NS1 mutant viruses (RSEV, GSEI, and EPEV) and a wild-type virus (PEQK) were generated from A/Swine/Shanghai/1/2005 virus and the pathogenicity of the viruses was determined in mice. The results showed that RSEV and PEQK viruses could not infect the mice. By contrast, GSEI and EPEV viruses could replicate in the lungs of mice without prior adaptation. The viral titers in lungs from GSEI and EPEV virus-infected mice were 2,300 and 7 pfu/g at fourth-day post-infection, respectively. Mild-to-moderate alveolitis was observed in the histopathological test of lungs from GSEI and EPEV virus-infected mice. The results indicated that C-terminal GSEI and EPEV motifs of NS1 protein involved in viral virulence and facilitated the A/Swine/Shanghai/1/2005 virus crossing the species barrier from swine to mice.
authors.affiliation: Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Jiangsu, People's Republic of China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Qi
authors.forename: Chengping
authors.initials: C
authors.lastname: Lu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D059386:Reverse Genetics; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D050505:Mutant Proteins; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors