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Regulation of host factor γ-H2AX level and location by enterovirus A71 for viral replication
- Source :
- Virulence, Vol 13, Iss 1, Pp 241-257 (2022)
- Publication Year :
- 2022
- Publisher :
- Taylor & Francis Group, 2022.
-
Abstract
- Numerous viruses manipulate host factors for viral production. We demonstrated that human enterovirus A71 (EVA71), a primary causative agent for hand, foot, and mouth disease (HFMD), increased the level of the DNA damage response (DDR) marker γ-H2AX. DDR is primarily mediated by the ataxia telangiectasia mutated (ATM), ATM and Rad3-related (ATR), or DNA-dependent protein kinase (DNA-PK) pathways. Upregulation of γ-H2AX by EVA71 was dependent on the ATR but not the ATM or DNA-PK pathway. As a nuclear factor, there is no previous evidence of cytoplasmic distribution of γ-H2AX. However, the present findings demonstrated that EVA71 encouraged the localization of γ-H2AX to the cytoplasm. Of note, γ-H2AX formed a complex with structural protein VP3, non-structural protein 3D, and the viral genome. Treatment with an inhibitor or CRISPR/Cas9 technology to decrease or silence the expression of γ-H2AX decreased viral genome replication in host cells; this effect was accompanied by decreased viral protein expression and virions. In animal experiments, caffeine was used to inhibit DDR; the results revealed that caffeine protected neonatal mice from death after infection with EVA71, laying the foundation for new therapeutic applications of caffeine. More importantly, in children with HFMD, γ-H2AX was upregulated in peripheral blood lymphocytes. The consistent in vitro and in vivo data on γ-H2AX from this study suggested that caffeine or other inhibitors of DDR might be novel therapeutic agents for HFMD.
Details
- Language :
- English
- ISSN :
- 21505594 and 21505608
- Volume :
- 13
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Virulence
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.627954e76db4f469511963af0e7b55d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/21505594.2022.2028482