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Virol Sin. 2018 Dec;33(6):531-537. doi: 10.1007/s12250-018-0072-8. Epub 2018 Dec 19.

The D253N Mutation in the Polymerase Basic 2 Gene in Avian Influenza (H9N2) Virus Contributes to the Pathogenesis of the Virus in Mammalian Hosts.

Author information

1
Laboratory Medicine Center, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, 528200, China.
2
Department of Respiratory Medicine, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, 528200, China.
3
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, China. ch02mkp@hku.hk.
4
HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. ch02mkp@hku.hk.

Abstract

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.

KEYWORDS:

Avian influenza virus; D253N; H9N2; Mammalian adaptation; Polymerase basic 2 (PB2)

PMID:
30569291
DOI:
10.1007/s12250-018-0072-8

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