| Autor: |
Li X; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People's Republic of China.; Department of Healthcare-associated Infection Management, Guizhou Provincial People's Hospital, Guiyang, People's Republic of China., Jia T; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People's Republic of China., Wang K; Department of Pathogen Biology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, People's Republic of China., Wang L; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People's Republic of China., Zhou L; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People's Republic of China., Li M; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People's Republic of China., Zhu W; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China., Shu Y; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, People's Republic of China.; Key Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China., Chen Y; Department of Pathogen Biology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, People's Republic of China. |
| Abstrakt: |
Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs. |
