The D253N Mutation in the Polymerase Basic 2 Gene in Avian Influenza (H9N2) Virus Contributes to the Pathogenesis of the Virus in Mammalian Hosts
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Mutations in the polymerase basic 2 (PB2) gene of avian influenza viruses are important signatures for their adaptation to mammalian hosts. Various adaptive mutations have been identified around the 627 and nuclear localization sequence (NLS) domains of PB2 protein, and these mutations contribute to the replicative ability of avian influenza viruses. However, few studies have focused on adaptive mutations in other regions of PB2. In this study, we investigated the functional roles of the D253N mutation in PB2 in an H9N2 virus. This mutation was found to affect an amino acid residue in the middle domain of the PB2 protein. The virus with the D253N mutation showed higher polymerase activity and transiently increased viral replication in human cells. However, the mutant did not show significant differences in viral replication in the respiratory tract of mice upon infection. Our results supported that the D253N mutation in the middle domain of PB2, similar to mutations at the 627 and NLS domains, specifically contributed to the replication of avian influenza viruses in human cells.
KeywordsAvian influenza virus Mammalian adaptation D253N Polymerase basic 2 (PB2) H9N2
This project was supported by the Science Research Project of the Guangdong Province (Grant no. 2016A050503047), Health and Medical Research Fund (Grant No. 12111832), Guangzhou Medical University High Level University Construction Project Funding and Research Grants Council of the Hong Kong Special Administrative Region, China, through the Theme Based Research Scheme (Ref: T11-705/14N).
JZ, RS, and CKPM designed the study, HA and CKPM performed the experiments; JZ, XJ, RJ, and YW analyzed the data, JZ and CKPM wrote the main manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
We declare that no authors have conflict interests.
Animal and Human Rights Statement
All institutional and national guidelines for the care and use of laboratory animals were followed.
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