Abstract
Zika virus (ZIKV) belongs to the Flaviviridae family and is related to other viruses that cause human diseases. Unlike other flaviviruses, ZIKV infection can cause congenital neurologic disorders and replicates efficiently in reproductive tissues1–3,. Here, we show that ZIKV envelope (E) protein is K63-linked polyubiquitinated by the E3-ubiquitin ligase TRIM7. Accordingly, ZIKV replicates less efficiently in brain and reproductive tissues of Trim7−/− mice. Ubiquitinated E is present on infectious Zika virions when released from specific cell types and enhances virus attachment and entry into cells. Specifically, K63-linked polyubiquitin chains directly interact with the Tim-1 (HAVCR1) receptor, enhancing virus replication in cells and in vivo in brain tissue. Recombinant ZIKV mutants lacking ubiquitination are attenuated in human cells and in a mouse model, but not in live mosquitoes. Monoclonal antibodies against K63-linked polyubiquitin specifically neutralize ZIKV and reduce viremia in mice. Collectively, the results demonstrate that ubiquitination of ZIKV E is an important determinant of virus entry, tropism and pathogenesis.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
