Virologica Sinica
14 August 2024
Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain
Xiu-Li Yana,b, Jian Lib,c, Qing-Qing Mab, Hong-Jiang Wangd, Lin Lib,c, Hui Zhaob, Cheng-Feng Qinb,✉, Xiao-Feng Lia,b,✉
a School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230032, China;
b Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, 100071, China;
c School of Medicine, Tsinghua University, Beijing, 100084, China;
d Department of Research, The Chinese People's Liberation Army Strategic Support Force Medical Center, Beijing, 100101, China
doi.org/10.1016/j.virs.2024.08.004
The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.
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