SERTAD3 induces proteasomal degradation of ZIKV capsid protein and represents a therapeutic target

Author:

Sun Nina123,Zhang Rong‐Rong4,Song Guang‐Yuan45,Cai Qiaomei23,Aliyari Saba R.6,Nielsen‐Saines Karin7,Jung Jae U.8,Yang Heng23,Cheng Genhong6ORCID,Qin Cheng‐Feng459ORCID

Affiliation:

1. Center of Systems Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

2. Institute of Systems Medicine Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

3. Suzhou Institute of Systems Medicine Suzhou Jiangsu China

4. State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China

5. School of Basic Medicine Anhui Medical University Hefei China

6. Department of Microbiology, Immunology and Molecular Genetics University of California Los Angeles California USA

7. Division of Pediatric Infectious Diseases, David Geffen School of Medicine University of California, Los Angeles Los Angeles California USA

8. Department of Cancer Biology and Global Center for Pathogens Research and Human Health, Lerner Research Institute Cleveland Clinic Cleveland Ohio USA

9. Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical Sciences Beijing China

Abstract

AbstractZika virus (ZIKV) is a mosquito‐borne RNA virus that belongs to the Flaviviridae family. While flavivirus replication is known to occur in the cytoplasm, a significant portion of the viral capsid protein localizes to the nucleus during infection. However, the role of the nuclear capsid is less clear. Herein, we demonstrated SERTA domain containing 3 (SERTAD3) as an antiviral interferon stimulatory gene product had an antiviral ability to ZIKV but not JEV. Mechanistically, we found that SERTAD3 interacted with the capsid protein of ZIKV in the nucleolus and reduced capsid protein abundance through proteasomal degradation. Furthermore, an eight amino acid peptide of SERTAD3 was identified as the minimum motif that binds with ZIKV capsid protein. Remarkably, the eight amino acids synthetic peptide from SERTAD3 significantly prevented ZIKV infection in culture and pregnant mouse models. Taken together, these findings not only reveal the function of SERTAD3 in promoting proteasomal degradation of a specific viral protein but also provide a promising host‐targeted therapeutic strategy against ZIKV infection.

Publisher

Wiley

Subject

Infectious Diseases,Virology

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