Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis.
The host Zinc finger antiviral protein (ZAP) has been reported exhibiting antiviral activity against positive-stranded RNA viruses (Togaviridae), negative-stranded RNA viruses (Filoviridae) and retroviruses (Retroviridae). However, whether ZAP restricts the infection of enterovirus and the development of enterovirus mediated disease remains unknown. Here, we reported the antiviral properties of ZAP against coxsackievirus B3 (CVB3), a single-stranded RNA virus of the Enterovirus genus within the Picornaviridae as a major causative agent of viral myocarditis (VMC). We found that the expression of ZAP was significantly induced after CVB3 infection in heart tissues of VMC mice. ZAP potently inhibited CVB3 replication in cells after infection, while overexpression of ZAP in mice significantly increased the resistance to CVB3 replication and viral myocarditis by significantly reducing cardiac inflammatory cytokine production. The ZAP-responsive elements (ZREs) were mapped to the 3'UTR and 5'UTR of viral RNA. Taken together, ZAP confers resistance to CVB3 infection via directly targeting viral RNA and protects mice from acute myocarditis by suppressing viral replication and cardiac inflammatory cytokine production. Our finding further expands ZAP's range of viral targets, and suggests ZAP as a potential therapeutic target for viral myocarditis caused by CVB3.
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Min
M
Li
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Kepeng
K
Yan
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Lin
L
Wei
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Jie
J
Yang
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Chenyu
C
Lu
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Fei
F
Xiong
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China.
Chunfu
C
Zheng
Institute of Biology and Medical Sciences, Soochow University, Building 703, 199 Ren-ai Road, Suzhou 215123, China. Electronic address: xuweifd828@126.com.
Wei
W
Xu
D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology* / Q000502:physiology; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011485:Protein Binding; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
D016207:Cytokines; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C577264:ZAP antiviral protein, mouse
Coxsackievirus B3; Viral myocarditis; Zinc finger antiviral protein