GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus
ABSTRACTInterferons (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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1677446 |
| _version_ | 1797385804141559808 |
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| author | Danying Chen Zhifei Hou Dong Jiang Mei Zheng Guoli Li Yue Zhang Rui Li Hanxin Lin Jinhong Chang Hui Zeng Ju-Tao Guo Xuesen Zhao |
| author_facet | Danying Chen Zhifei Hou Dong Jiang Mei Zheng Guoli Li Yue Zhang Rui Li Hanxin Lin Jinhong Chang Hui Zeng Ju-Tao Guo Xuesen Zhao |
| author_sort | Danying Chen |
| collection | DOAJ |
| description | ABSTRACTInterferons (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. |
| first_indexed | 2024-03-08T21:59:38Z |
| format | Article |
| id | doaj.art-f22fd231b9944beba50e35e378fd1e9b |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-08T21:59:38Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-f22fd231b9944beba50e35e378fd1e9b2023-12-19T16:09:58ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811511152310.1080/22221751.2019.1677446GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virusDanying Chen0Zhifei Hou1Dong Jiang2Mei Zheng3Guoli Li4Yue Zhang5Rui Li6Hanxin Lin7Jinhong Chang8Hui Zeng9Ju-Tao Guo10Xuesen Zhao11Institute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaDepartment of Pathology and Laboratory Medicine, Western University, London, Ontario, CanadaBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USAInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USAInstitute of Infectious disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaABSTRACTInterferons (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.https://www.tandfonline.com/doi/10.1080/22221751.2019.1677446Interferon-stimulated genes (ISGs)GILTSARS-CoVEbola virusLassa fever virus |
| spellingShingle | Danying Chen Zhifei Hou Dong Jiang Mei Zheng Guoli Li Yue Zhang Rui Li Hanxin Lin Jinhong Chang Hui Zeng Ju-Tao Guo Xuesen Zhao GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus Emerging Microbes and Infections Interferon-stimulated genes (ISGs) GILT SARS-CoV Ebola virus Lassa fever virus |
| title | GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus |
| title_full | GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus |
| title_fullStr | GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus |
| title_full_unstemmed | GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus |
| title_short | GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus |
| title_sort | gilt restricts the cellular entry mediated by the envelope glycoproteins of sars cov ebola virus and lassa fever virus |
| topic | Interferon-stimulated genes (ISGs) GILT SARS-CoV Ebola virus Lassa fever virus |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1677446 |
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