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Journal article
GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus
Emerging microbes & infections, v 8(1), pp 1511-1523
01 Jan 2019
PMID: 31631785
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses. Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon. While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins. Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry. We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes. Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
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Details
- Title
- GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus
- Creators
- Danying Chen - Beijing Key Laboratory of Emerging Infectious DiseaseZhifei Hou - Department of Pulmonary and Critical Care Medicine, General Hospital of Datong Coal Mine Group Co., LtdDong Jiang - Beijing Key Laboratory of Emerging Infectious DiseaseMei Zheng - Beijing Key Laboratory of Emerging Infectious DiseaseGuoli Li - Beijing Key Laboratory of Emerging Infectious DiseaseYue Zhang - Beijing Key Laboratory of Emerging Infectious DiseaseRui Li - Beijing Key Laboratory of Emerging Infectious DiseaseHanxin Lin - Department of Pathology and Laboratory Medicine, Western UniversityJinhong Chang - Baruch S. Blumberg InstituteHui Zeng - Beijing Key Laboratory of Emerging Infectious DiseaseJu-Tao Guo - Baruch S. Blumberg InstituteXuesen Zhao - Beijing Key Laboratory of Emerging Infectious Disease
- Publication Details
- Emerging microbes & infections, v 8(1), pp 1511-1523
- Publisher
- Taylor & Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000491359200001
- Scopus ID
- 2-s2.0-85073607180
- Other Identifier
- 991020547446404721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Microbiology