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Updated: Oct 15, 2025
Isolation and Quantification of Zika Virus from Multiple Organs in a Mouse
Published on: August 15, 2019
USP38 Inhibits Zika Virus Infection by Removing Envelope Protein Ubiquitination
Yingchong Wang1, Qin Li1, Dingwen Hu1
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
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.
Insights
The ubiquitin-specific peptidase 38 (USP38) protein helps the body fight Zika virus (ZIKV) infection. USP38 inhibits ZIKV by reducing viral protein ubiquitination, offering a potential therapeutic target.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Zika virus (ZIKV) causes severe neurodegenerative and congenital disorders.
- Understanding ZIKV infection mechanisms is crucial for developing treatments.
Purpose of the Study:
- To identify host factors involved in ZIKV resistance.
- To elucidate the mechanism by which USP38 confers resistance to ZIKV.
Main Methods:
- Investigated the role of ubiquitin-specific peptidase 38 (USP38) in ZIKV infection.
- Analyzed USP38 interaction with ZIKV envelope (E) protein.
- Assessed the impact of USP38 deubiquitinase activity on ZIKV replication.
Main Results:
- USP38 expression is unaffected by ZIKV infection.
- USP38 binds to the ZIKV E protein via its C-terminal domain.
- USP38 attenuates K48- and K63-linked polyubiquitination of the ZIKV E protein, repressing infection.
- Deubiquitinase activity of USP38 is essential for inhibiting ZIKV infection.
Conclusions:
- USP38 is a novel host factor that confers resistance to ZIKV infection.
- USP38 inhibits ZIKV by deubiquitinating the viral E protein.
- USP38 represents a potential therapeutic target for ZIKV prevention and treatment.
