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https://doi.org/10.1128/jvi.01055-21
Title: | A novel attenuated enterovirus A71 mutant with VP1-V238A, K244R exhibits reduced efficiency of cell entry/exit and augmented binding affinity to sulfated glycans | Authors: | Meng, Tao Wong, Sek-Man Chua, Kaw-Bing |
Keywords: | Cell-adapted mutants Enterovirus A71 Live attenuated vaccines Sulfated glycans Virulence determinants Virus dissemination Virus entry/exit |
Issue Date: | 1-Sep-2021 | Publisher: | American Society for Microbiology | Citation: | Meng, Tao, Wong, Sek-Man, Chua, Kaw-Bing (2021-09-01). A novel attenuated enterovirus A71 mutant with VP1-V238A, K244R exhibits reduced efficiency of cell entry/exit and augmented binding affinity to sulfated glycans. Journal of Virology 95 (22) : e01055-21. ScholarBank@NUS Repository. https://doi.org/10.1128/jvi.01055-21 | Rights: | Attribution 4.0 International | Abstract: | Enterovirus A71 (EV-A71) is one of the major etiological agents of hand, foot, and mouth disease (HFMD), and infection occasionally leads to fatal neurological complications in children. However, only inactivated whole-virus vaccines against EV-A71 are commercially available in Mainland China. Furthermore, the mechanisms underlying the infectivity and pathogenesis of EV-A71 remain to be better understood. By adaptation of an EV-A71 B5 strain in monkey Vero cells in the presence of brilliant black BN (E151), an anti-EV-A71 agent, a double mutant with VP1-V238A,K244R emerged whose infection was enhanced by E151. The growth of the reverse genetics (RG) mutant RG/B5-VP1-V238A,K244R (RG/B5-AR) was promoted by E151 in Vero cells but inhibited in other human and murine cells, while its parental wild type, RG/B5-wt, was strongly prevented by E151 from infection in all tested cells. In the absence of E151, RG/B5-AR exhibited defective cell entry/exit, resulting in reduced viral transmission and growth in vitro. It had augmented binding affinity to sulfated glycans, cells, and tissue/organs, which probably functioned as decoys to restrict viral dissemination and infection. RG/B5-AR was also attenuated, with a 355 times higher 50% lethal dose (LD50) and a shorter timing of virus clearance than those of RG/B5-wt in suckling AG129 mice. However, it remained highly immunogenic in adult AG129 mice and protected their suckling mice from lethal EV-A71 challenges through maternal neutralizing antibodies. Overall, discovery of the attenuated mutant RG/B5-AR contributes to better understanding of virulence determinants of EV-A71 and to further development of novel vaccines against EV-A71. Copyright © 2021 Meng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. | Source Title: | Journal of Virology | URI: | https://scholarbank.nus.edu.sg/handle/10635/233825 | ISSN: | 0022-538X | DOI: | 10.1128/jvi.01055-21 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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