Abstract
H9N2 influenza viruses have been circulating worldwide in multiple avian species and have repeatedly infected humans to cause typical disease. The continued avian-to-human interspecies transmission of H9N2 viruses raises concerns about the possibility of viral adaption with increased virulence for humans. To investigate the genetic basis of H9N2 influenza virus host range and pathogenicity in mammals, we generated a mouse-adapted H9N2 virus (SD16-MA) that possessed significantly higher virulence than wide-type virus (SD16). Increased virulence was detectable after 8 sequential lung passages in mice. Five amino acid substitutions were found in the genome of SD16-MA compared with SD16 virus: PB2 (M147L, V250G and E627K), HA (L226Q) and M1 (R210K). Assessments of replication in mice showed that all of the SD16-MA PB2, HA and M1 genome segments increased virus replication; however, only the mouse-adapted PB2 significantly increased virulence. Although the PB2 E627K amino acid substitution enhanced viral polymerase activity and replication, none of the single mutations of mouse adapted PB2 could confer increased virulence on the SD16 backbone. The combination of M147L and E627K significantly enhanced viral replication ability and virulence in mice. Thus, our results show that the combination of PB2 amino acids at position 147 and 627 is critical for the increased pathogenicity of H9N2 influenza virus in mammalian host.
Highlights
H9N2 influenza viruses circulate worldwide and are endemic in multiple terrestrial avian species in Asia [1,2,3,4]
The present results showed that adapted virus could be obtained by serial passages and PB2 gene of SD16-MA is critical for the virulence of mouse-adapted H9N2 influenza virus, especially, the combination of PB2 M147L
The amino acid at position 627 of the PB2 protein has been described as a host range determinant, and the mutation E627K has been shown to be a key factor in the adaptation of H5N1 [23,24,25] or other avian subtypes [49,50] influenza viruses to mammals
Summary
H9N2 influenza viruses circulate worldwide and are endemic in multiple terrestrial avian species in Asia [1,2,3,4]. It is noteworthy that H9N2 influenza viruses in poultry have occasionally been transmitted to mammalian species, including humans and pigs [5,6,7,8,9]. Human H9N2 infections produce a typical human flu-like illness that can go undetected [6,11,14], providing the viruses a greater opportunity to adapt to humans. These observations raise concerns about the possibility of H9N2 viruses evolving into pandemic strains
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
