[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Sci Rep. 2018 Aug 30;8(1):13066. doi: 10.1038/s41598-018-31397-3.
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates.
Arai Y1,2, Kawashita N3,4, Hotta K5,6, Hoang PVM7, Nguyen HLK7, Nguyen TC7, Vuong CD7, Le TT7, Le MTQ7, Soda K8, Ibrahim MS9, Daidoji T1, Takagi T4, Shioda T2, Nakaya T1, Ito T8, Hasebe F5, Watanabe Y10,11.
Author information: 1 Department of Infectious Diseases, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan. 2 Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 3 Graduate School of Science and Engineering, Kindai University, Osaka, Japan. 4 Graduate School of Pharmaceutical Science, Osaka University, Osaka, Japan. 5 Vietnam Research Station, Center for Infectious Disease Research in Asia and Africa, Institute of Tropical Medicine, Nagasaki University, Hanoi, Vietnam. 6 Laboratory of Veterinary Public Health, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. 7 Department of Virology, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam. 8 Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori, Japan. 9 Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt. 10 Department of Infectious Diseases, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan. firstname.lastname@example.org. 11 Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. email@example.com.
The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 126.96.36.199 and clade 2.3.4 strains isolated from 2008-2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.
PMID: 30166556 PMCID: PMC6117316 DOI: 10.1038/s41598-018-31397-3 [Indexed for MEDLINE] Free PMC Article
Keywords: Avian Influenza; H5N1; Human; Asian Region.