Journal article
Envelope protein ubiquitination drives entry and pathogenesis of Zika virus
Nature (London), Vol.585(7825), pp.414-419
09/2020
DOI: 10.1038/s41586-020-2457-8
PMCID: PMC7501154
PMID: 32641828
Abstract
Zika virus (ZIKV) belongs to the family Flaviviridae, and is related to other viruses that cause human diseases. Unlike other flaviviruses, ZIKV infection can cause congenital neurological disorders and replicates efficiently in reproductive tissues
. Here we show that the envelope protein (E) of ZIKV is polyubiquitinated by the E3 ubiquitin ligase TRIM7 through Lys63 (K63)-linked polyubiquitination. Accordingly, ZIKV replicates less efficiently in the brain and reproductive tissues of Trim7
mice. Ubiquitinated E is present on infectious virions of ZIKV when they are released from specific cell types, and enhances virus attachment and entry into cells. Specifically, K63-linked polyubiquitin chains directly interact with the TIM1 (also known as HAVCR1) receptor of host cells, which enhances virus entry in cells as well as in brain tissue in vivo. Recombinant ZIKV mutants that lack ubiquitination are attenuated in human cells and in wild-type mice, but not in live mosquitoes. Monoclonal antibodies against K63-linked polyubiquitin specifically neutralize ZIKV and reduce viraemia in mice. Our results demonstrate that the ubiquitination of ZIKV E is an important determinant of virus entry, tropism and pathogenesis.
Details
- Title: Subtitle
- Envelope protein ubiquitination drives entry and pathogenesis of Zika virus
- Creators
- Maria I Giraldo - University of QuindíoHongjie Xia - The University of Texas Medical Branch at GalvestonLeopoldo Aguilera-Aguirre - The University of Texas Medical Branch at GalvestonAdam Hage - The University of Texas Medical Branch at GalvestonSarah van Tol - The University of Texas Medical Branch at GalvestonChao Shan - The University of Texas Medical Branch at GalvestonXuping Xie - The University of Texas Medical Branch at GalvestonGail L Sturdevant - National Institute of Allergy and Infectious DiseasesShelly J Robertson - National Institute of Allergy and Infectious DiseasesKristin L McNally - National Institute of Allergy and Infectious DiseasesKimberly Meade-White - National Institute of Allergy and Infectious DiseasesSasha R Azar - The University of Texas Medical Branch at GalvestonShannan L Rossi - The University of Texas Medical Branch at GalvestonWendy Maury - University of IowaMichael Woodson - The University of Texas Medical Branch at GalvestonHolly Ramage - University of PennsylvaniaJeffrey R Johnson - University of California, San FranciscoNevan J Krogan - University of California, San FranciscoMarc C Morais - The University of Texas Medical Branch at GalvestonSonja M Best - National Institute of Allergy and Infectious DiseasesPei-Yong Shi - The University of Texas Medical Branch at GalvestonRicardo Rajsbaum - The University of Texas Medical Branch at Galveston
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.585(7825), pp.414-419
- DOI
- 10.1038/s41586-020-2457-8
- PMID
- 32641828
- PMCID
- PMC7501154
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Grant note
- R01 AI127744 / NIAID NIH HHS UL1 TR001439 / NCATS NIH HHS R21 AI126012 / NIAID NIH HHS K12 HD052023 / NICHD NIH HHS AI145617 / NIH HHS R21 AI132479 / NIAID NIH HHS R01 AI134907 / NIAID NIH HHS R41 AI136126 / NIAID NIH HHS T32 AI060549 / NIAID NIH HHS U19 AI142759 / NIAID NIH HHS U19 AI118610 / NIAID NIH HHS
- Language
- English
- Date published
- 09/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297315102771
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