Author:
Rattanakomol Patthaya,Srimanote Potjanee,Tongtawe Pongsri,Khantisitthiporn Onruedee,Supasorn Oratai,Thanongsaksrikul Jeeraphong
Abstract
AbstractEnterovirus A71 (EV-A71) causes hand, foot, and mouth disease associated with neurological complications in young children. Currently, there is no specific treatment for EV-A71 infection due to the inadequate information on viral biology and neuropathogenesis. Among enteroviruses, nonstructural 3A protein mediates the formation of replication organelles which plays a major role in viral RNA synthesis and assembly. Although enteroviral 3A proteins have been intensively studied, the data on EV-A71 3A, especially in neuronal cells, are still limited. In this study, PRSS3 (mesotrypsinogen, also known as brain trypsinogen) was identified as EV-A71 3A-interacting counterpart from the transfected human neuroblastoma SH-SY5Y cells by pull-down assay and liquid chromatography tandem mass spectrometry. It was confirmed that PRSS3 variant 3 derived from human SH-SY5Y cells had the physical interaction with EV-A71 3A. Importantly, the role of PRSS3 in EV-A71 replication was verified by overexpression and siRNA-mediated gene silencing approaches. The detailed mechanism of the PRSS3 involved in EV-A71 replication and neuropathogenesis warrants further experimental elucidation. In conclusion, this study has discovered a novel EV-A71 3A interacting protein that offers the opportunity to study the neuropathogenesis of the infection which paves the way for developing a specific and effective treatment for the disease.
Funder
the Thammasat University Ph.D. scholarship
Program Management Unit for Human Resources & Institutional Development, Research and Innovation, the Office of National Higher Education Science Research and Innovation Policy Council
the Thammasat University Research Unit in Molecular Pathogenesis and Immunology of Infectious Diseases
Publisher
Springer Science and Business Media LLC
Reference62 articles.
1. Zhang, Y. et al. An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong. China. J. Clin. Virol. 44, 262–267. https://doi.org/10.1016/j.jcv.2009.02.002 (2009).
2. Ma, E., Chan, K. C., Cheng, P., Wong, C. & Chuang, S. K. The enterovirus 71 epidemic in 2008—public health implications for Hong Kong. Int. J. Infect. Dis. 14, e775–e780. https://doi.org/10.1016/j.ijid.2010.02.2265 (2010).
3. Wang, J. R. et al. Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000. J. Clin. Microbiol. 40, 10–15. https://doi.org/10.1128/JCM.40.1.10-15.2002 (2002).
4. Fujimoto, T. et al. Outbreak of central nervous system disease associated with hand, foot, and mouth disease in Japan during the summer of 2000: Detection and molecular epidemiology of enterovirus 71. Microbiol. Immunol. 46, 621–627. https://doi.org/10.1111/j.1348-0421.2002.tb02743.x (2002).
5. Shekhar, K. et al. Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia–clinical and pathological characteristics. Med. J. Malaysia 60, 297–304 (2005).
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