USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination |
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| Authors: | Yingchong Wang Qin Li Dingwen Hu Daolong Gao Wenbiao Wang Kailang Wu Jianguo Wu |
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| Affiliation: | 1.State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; (Y.W.); (Q.L.); (D.H.); (K.W.);2.Guangdong Longfan Biological Science and Technology Company, Shunde District, Foshan 528315, China;3.Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China;4.Foshan Institute of Medical Microbiology, Foshan 528315, China |
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| Abstract: | Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South America has caused severe human congenital and neurologic disorders. Thus, it is vitally important to determine the inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to the ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost the ability to inhibit infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection. |
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| Keywords: | deubiquitinase envelope protein USP38 virus infection Zika virus |
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