Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion
Abstract Background Viral infection elicits the type I interferon (IFN-I) response in host cells and subsequently inhibits viral infection through inducing hundreds of IFN-stimulated genes (ISGs) that counteract many steps in the virus life cycle. However, most of ISGs have unclear functions and mec...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-024-01202-y |
| _version_ | 1797273119658868736 |
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| author | Qiaomei Cai Nina Sun Yurui Zhang Jingfeng Wang Chaohu Pan Yu Chen Lili Li Xiaorong Li Wancheng Liu Saba R. Aliyari Heng Yang Genhong Cheng |
| author_facet | Qiaomei Cai Nina Sun Yurui Zhang Jingfeng Wang Chaohu Pan Yu Chen Lili Li Xiaorong Li Wancheng Liu Saba R. Aliyari Heng Yang Genhong Cheng |
| author_sort | Qiaomei Cai |
| collection | DOAJ |
| description | Abstract Background Viral infection elicits the type I interferon (IFN-I) response in host cells and subsequently inhibits viral infection through inducing hundreds of IFN-stimulated genes (ISGs) that counteract many steps in the virus life cycle. However, most of ISGs have unclear functions and mechanisms in viral infection. Thus, more work is required to elucidate the role and mechanisms of individual ISGs against different types of viruses. Results Herein, we demonstrate that poliovirus receptor-like protein4 (PVRL4) is an ISG strongly induced by IFN-I stimulation and various viral infections. Overexpression of PVRL4 protein broadly restricts growth of enveloped RNA and DNA viruses, including vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whereas deletion of PVRL4 in host cells increases viral infections. Mechanistically, it suppresses viral entry by blocking viral-cellular membrane fusion through inhibiting endosomal acidification. The vivo studies demonstrate that Pvrl4-deficient mice were more susceptible to the infection of VSV and IAV. Conclusion Overall, our studies not only identify PVRL4 as an intrinsic broad-spectrum antiviral ISG, but also provide a candidate host-directed target for antiviral therapy against various viruses including SARS-CoV-2 and its variants in the future. |
| first_indexed | 2024-03-07T14:39:03Z |
| format | Article |
| id | doaj.art-abf55842bbbb44ba9ea50a937817633c |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-03-07T14:39:03Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-abf55842bbbb44ba9ea50a937817633c2024-03-05T20:28:58ZengBMCCell & Bioscience2045-37012024-02-0114111710.1186/s13578-024-01202-yInterferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusionQiaomei Cai0Nina Sun1Yurui Zhang2Jingfeng Wang3Chaohu Pan4Yu Chen5Lili Li6Xiaorong Li7Wancheng Liu8Saba R. Aliyari9Heng Yang10Genhong Cheng11National Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Microbiology and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases of the First Affiliated Hospital, Zhejiang University School of MedicineNational Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNational Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNational Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeClinical Microbiology and Immunology, Affiliated Hospital of Guizhou Medical UniversityNational Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeNational Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Hematology, Qilu Hospital of Shandong UniversityDepartment of Microbiology, Immunology and Molecular Genetics, University of CaliforniaNational Key Laboratory of Immunity and Inflammation, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Microbiology, Immunology and Molecular Genetics, University of CaliforniaAbstract Background Viral infection elicits the type I interferon (IFN-I) response in host cells and subsequently inhibits viral infection through inducing hundreds of IFN-stimulated genes (ISGs) that counteract many steps in the virus life cycle. However, most of ISGs have unclear functions and mechanisms in viral infection. Thus, more work is required to elucidate the role and mechanisms of individual ISGs against different types of viruses. Results Herein, we demonstrate that poliovirus receptor-like protein4 (PVRL4) is an ISG strongly induced by IFN-I stimulation and various viral infections. Overexpression of PVRL4 protein broadly restricts growth of enveloped RNA and DNA viruses, including vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whereas deletion of PVRL4 in host cells increases viral infections. Mechanistically, it suppresses viral entry by blocking viral-cellular membrane fusion through inhibiting endosomal acidification. The vivo studies demonstrate that Pvrl4-deficient mice were more susceptible to the infection of VSV and IAV. Conclusion Overall, our studies not only identify PVRL4 as an intrinsic broad-spectrum antiviral ISG, but also provide a candidate host-directed target for antiviral therapy against various viruses including SARS-CoV-2 and its variants in the future.https://doi.org/10.1186/s13578-024-01202-yIFN-IPVRL4Viral entryMembrane fusion |
| spellingShingle | Qiaomei Cai Nina Sun Yurui Zhang Jingfeng Wang Chaohu Pan Yu Chen Lili Li Xiaorong Li Wancheng Liu Saba R. Aliyari Heng Yang Genhong Cheng Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion Cell & Bioscience IFN-I PVRL4 Viral entry Membrane fusion |
| title | Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion |
| title_full | Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion |
| title_fullStr | Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion |
| title_full_unstemmed | Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion |
| title_short | Interferon-stimulated gene PVRL4 broadly suppresses viral entry by inhibiting viral-cellular membrane fusion |
| title_sort | interferon stimulated gene pvrl4 broadly suppresses viral entry by inhibiting viral cellular membrane fusion |
| topic | IFN-I PVRL4 Viral entry Membrane fusion |
| url | https://doi.org/10.1186/s13578-024-01202-y |
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