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dc.contributor.authorLei, X.
dc.contributor.authorHan, N.
dc.contributor.authorXiao, X.
dc.contributor.authorJin, Q.
dc.contributor.authorHe, B.
dc.contributor.authorWang, J.
dc.date.accessioned2016-01-28T23:01:43Z
dc.date.available2016-01-28T23:01:43Z
dc.date.issued2014-09-01
dc.identifier.bibliographicCitationLei, Xiaobo, et al. "Enterovirus 71 3C inhibits cytokine expression through cleavage of the TAK1/TAB1/TAB2/TAB3 complex." Journal of virology 88.17 (2014): 9830-9841. DOI: 10.1128/JVI.01425-14.en_US
dc.identifier.issn0022-538X
dc.identifier.urihttp://hdl.handle.net/10027/20067
dc.descriptionThis is the copy of an article published in the Journal of Virology © 2014 American Society for Microbiology.en_US
dc.description.abstractEnterovirus 71 (EV71) causes hand, foot, and mouth disease in young children and infants. Severe infection with EV71 can lead to various neurological complications or fatal diseases. However, the mechanism of EV71 pathogenesis is poorly understood. Emerging evidence suggests that EV71 modulates type I interferon (IFN) and cytokine responses. Here, we show that EV71 disables components of the TAB2 complex through the 3C protein. When expressed in mammalian cells, EV71 3C interacts with TAB2 and TAK1, which inhibits NF-B activation. Furthermore, 3C mediates cleavage of TAB2 and its partners, which requires the protease activity. H40D or C147S substitution in the 3C active sites abolishes its activity, whereas R84Q or V154S substitution in the RNA binding domain has no effect. The 3C protein targets TAB2 at Q113-S114, TAK1 at Q360-S361, TAB1 both at Q414-G415 and Q451-S452, and TAB3 at Q173-G174 and Q343-G344. Importantly, overexpression of TAB2 inhibits EV71 replication, whereas addition of cleaved fragments has no effect. Thus, an equilibrium between the TAB2 complex and EV71 3C represents a control point of viral infection. These results suggest that TAK1/TAB1/TAB2/TAB3 cleavage mediated by EV71 may be a mechanism to interfere with inflammatory responses.en_US
dc.description.sponsorshipThis work was supported by grants from the National Basic Research Program of China (973 Project, 2011CB504903), the Chinese National Health and Family Planning Commission Grant (201302006-05), the National Science Foundation for Outstanding Young Scientists (81225014), the National Natural Science Foundation of China (31270200), an intramural grant from the Institute of Pathogen Biology, Chinese Academy of Medical Sciences (2013IPB401), the Program for Changjiang Scholars and Innovative Research Team in University (IRT13007), and the National Institute of Allergy and Infectious Diseases of the United States (AI092230).en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.titleEnterovirus 71 3C inhibits cytokine expression through cleavage of the TAK1/TAB1/TAB2/TAB3 complex.en_US
dc.typeArticleen_US


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