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Adaptive mutations in PB2 gene contribute to the high virulence of a natural reassortant H5N2 avian influenza virus in mice.
Virus Res. 2015 Dec 02; 210:255-63.VR

Abstract

The highly pathogenic A/chicken/Hebei/1102/2010 (HB10) H5N2 virus is a natural reassortant derived from circulating H5N1 and endemic H9N2 avian influenza viruses (AIV). To evaluate the potential of its interspecies transmission, we previously serially passaged the non-virulent HB10 virus in the mouse lung and obtained a high virulence variant (HB10-MA). Genomic sequencing revealed five mutations (HA-S227N, PB2-Q591K, PB2-D701N, PA-I554V and NP-R351K) that distinguished HB10-MA virus from its parental HB10 virus. In this study, we further investigated the molecular basis for the enhanced virulence of HB10-MA in mice. By generating a series of reassortants between the two viruses and evaluating their virulence in mice, we found that both PB2 and PA genes contribute to the high virulence of HB10-MA in mice, whereas PB2 gene carrying the 591K and/or 701N had a dominant function. In addition, the two amino acids showed a cumulative effect on the virulence, virus replication, and polymerase activity of HB10 or HB10-MA. Therefore, our results collectively emphasized the crucial role of PB2 gene, particularly the paired mutations of Q591K and D701N in the host adaptation of the novel reassortant H5N2 AIV in mammals, which may provide helpful insights into the pathogenic potential of emerging AIV in human beings.

Authors+Show Affiliations

Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China. Electronic address: xxl@yzu.edu.cn.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China.Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China. Electronic address: xfliu@yzu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26315686

Citation

Li, Qunhui, et al. "Adaptive Mutations in PB2 Gene Contribute to the High Virulence of a Natural Reassortant H5N2 Avian Influenza Virus in Mice." Virus Research, vol. 210, 2015, pp. 255-63.
Li Q, Wang X, Sun Z, et al. Adaptive mutations in PB2 gene contribute to the high virulence of a natural reassortant H5N2 avian influenza virus in mice. Virus Res. 2015;210:255-63.
Li, Q., Wang, X., Sun, Z., Hu, J., Gao, Z., Hao, X., Li, J., Liu, H., Wang, X., Gu, M., Xu, X., Liu, X., & Liu, X. (2015). Adaptive mutations in PB2 gene contribute to the high virulence of a natural reassortant H5N2 avian influenza virus in mice. Virus Research, 210, 255-63. https://doi.org/10.1016/j.virusres.2015.08.017
Li Q, et al. Adaptive Mutations in PB2 Gene Contribute to the High Virulence of a Natural Reassortant H5N2 Avian Influenza Virus in Mice. Virus Res. 2015 Dec 2;210:255-63. PubMed PMID: 26315686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adaptive mutations in PB2 gene contribute to the high virulence of a natural reassortant H5N2 avian influenza virus in mice. AU - Li,Qunhui, AU - Wang,Xuan, AU - Sun,Zhongtao, AU - Hu,Jiao, AU - Gao,Zhao, AU - Hao,Xiaoli, AU - Li,Juan, AU - Liu,Huimou, AU - Wang,Xiaoquan, AU - Gu,Min, AU - Xu,Xiulong, AU - Liu,Xiaowen, AU - Liu,Xiufan, Y1 - 2015/08/24/ PY - 2015/03/10/received PY - 2015/08/06/revised PY - 2015/08/21/accepted PY - 2015/8/29/entrez PY - 2015/9/1/pubmed PY - 2016/8/19/medline KW - Avian influenza virus KW - H5N2 KW - H7N9 KW - Mouse-adapted KW - PB2 KW - Pathogenicity KW - Reassortant SP - 255 EP - 63 JF - Virus research JO - Virus Res VL - 210 N2 - The highly pathogenic A/chicken/Hebei/1102/2010 (HB10) H5N2 virus is a natural reassortant derived from circulating H5N1 and endemic H9N2 avian influenza viruses (AIV). To evaluate the potential of its interspecies transmission, we previously serially passaged the non-virulent HB10 virus in the mouse lung and obtained a high virulence variant (HB10-MA). Genomic sequencing revealed five mutations (HA-S227N, PB2-Q591K, PB2-D701N, PA-I554V and NP-R351K) that distinguished HB10-MA virus from its parental HB10 virus. In this study, we further investigated the molecular basis for the enhanced virulence of HB10-MA in mice. By generating a series of reassortants between the two viruses and evaluating their virulence in mice, we found that both PB2 and PA genes contribute to the high virulence of HB10-MA in mice, whereas PB2 gene carrying the 591K and/or 701N had a dominant function. In addition, the two amino acids showed a cumulative effect on the virulence, virus replication, and polymerase activity of HB10 or HB10-MA. Therefore, our results collectively emphasized the crucial role of PB2 gene, particularly the paired mutations of Q591K and D701N in the host adaptation of the novel reassortant H5N2 AIV in mammals, which may provide helpful insights into the pathogenic potential of emerging AIV in human beings. SN - 1872-7492 UR - https://www.unboundmedicine.com/medline/citation/26315686/Adaptive_mutations_in_PB2_gene_contribute_to_the_high_virulence_of_a_natural_reassortant_H5N2_avian_influenza_virus_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-1702(15)30049-6 DB - PRIME DP - Unbound Medicine ER -