Novel virulence determinants in VP1 regulate the assembly of enterovirus-A71
EV-A71 causes hand, foot, and mouth disease in children. In this study, we discovered three highly conserved residues at positions 75, 78, and 88 of the capsid protein VP1 as the potential virulence determinants of EV-A71, which can influence viral replication by regulating the assembly of EV-A71. Mechanistic studies revealed that VP1-T75A could affect the maturation cleavage of the VP0 precursor, resulting in deficiencies in binding to the receptor SCARB2, viral attachment, internalization, and even uncoating. For the mutants of T78A and G88A, more noninfectious empty particles were produced during viral assembly. The discovery of these novel determinants of EV-A71 virulence will promote the study of the pathogenesis of enteroviruses.
Authors
- Quanjie Li (ORCID: https://orcid.org/0000-0002-4151-0627)
- Dongrong Yi (ORCID: https://orcid.org/0009-0009-9903-2734)
- Shan Cen (ORCID: https://orcid.org/0000-0003-3358-0411)
- Saisai Guo
- Yongcheng Ren (ORCID: https://orcid.org/0000-0002-8673-4640)
- Ruifang Zheng (ORCID: https://orcid.org/0000-0002-1287-5029)
- Jing Wang (ORCID: https://orcid.org/0000-0001-9259-697X)
- Ao Zhang (ORCID: https://orcid.org/0000-0001-7185-4642)
- Xiaoyu Li (ORCID: https://orcid.org/0009-0008-8894-030X)
- Ling Ma (ORCID: https://orcid.org/0009-0003-9731-059X)
- Rui Zhou (ORCID: https://orcid.org/0000-0002-9986-3468)
- Jiwei Ding (ORCID: https://orcid.org/0000-0003-1942-4885)
- Jianyuan Zhao
- Tingting Sun
- G. Liu
- Yongxin Zhang (ORCID: https://orcid.org/0000-0003-0950-9455)
- Wenjing Zhang (ORCID: https://orcid.org/0009-0007-3194-8741)
- Qian Liu (ORCID: https://orcid.org/0000-0001-5341-1290)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Xinjiang Institute of Materia Medica (CN)
Publication Details
- Journal
- Journal of Virology
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1128/jvi.01655-24
- Citations
- 4
- Primary Topic
- Viral Infections and Immunology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Chinese Academy of Medical Sciences
- National Medical Research Council
- Chinese Academy of Medical Sciences Initiative for Innovative Medicine