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SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3D pol protein via the ubiquitin-proteasome pathway.
- Source :
-
Journal of medical virology [J Med Virol] 2023 Aug; Vol. 95 (8), pp. e29030. - Publication Year :
- 2023
-
Abstract
- Enterovirus A71 (EV-A71) is a highly contagious virus that poses a major threat to global health, representing the primary etiological agent for hand-foot and mouth disease (HFMD) and neurological complications. It has been established that interferon signaling is critical to establishing a robust antiviral state in host cells, mainly mediated through the antiviral effects of numerous interferon-stimulated genes (ISGs). The host restriction factor SHFL is a novel ISG with broad antiviral activity against various viruses through diverse underlying molecular mechanisms. Although SHFL is widely acknowledged for its broad-spectrum antiviral activity, it remains elusive whether SHFL inhibits EV-A71. In this work, we validated that EV-A71 triggers the upregulation of SHFL both in cell lines and in a mouse model. Knockdown and overexpression of SHFL in EVA71-infected cells suggested that this factor could markedly suppress EV-A71 replication. Our findings further revealed an intriguing mechanism of SHFL that it could interact with the nonstructural proteins 3D <superscript>pol</superscript> of EV-A71 and promoted the degradation of 3D <superscript>pol</superscript> through the ubiquitin-proteasome pathway. Furthermore, the zinc-finger domain and the 36 amino acids (164-199) of SHFL were crucial to the interaction between SHFL and EV-A71 3D <superscript>pol</superscript> . Overall, these findings broadened our understanding of the pivotal roles of SHFL in the interaction between the host and EV-A71.<br /> (© 2023 Wiley Periodicals LLC.)
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 95
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 37565734
- Full Text :
- https://doi.org/10.1002/jmv.29030