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

作     者：Jinfeng Zhang Rong Su Xiaoyun Jian Hongliang An Ronbing Jiang Chris Ka Pun Mok 

作者机构：Laboratory Medicine Center Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine Department of Respiratory Medicine Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine 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 HKU-Pasteur Research Pole School of Public Health HKU Li Ka Shing Faculty of Medicine The University of Hong Kong 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2018年第33卷第6期

页      面：531-537页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：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 Research Grants Council of the Hong Kong Special Administrative Region, China, through the Theme Based Research Scheme (Ref: T11-705/14N) 

主　　题：Avian influenza virus Mammalian adaptation D253N Polymerase basic 2(PB2) H9N2 

摘      要：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.