Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity
Viral inclusion bodies (IBs) commonly form during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK1) or IκB kinase epsilon (IKKε), wa...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/88122 |
| _version_ | 1797339267794468864 |
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| author | Lin Zhu Jing Jin Tingting Wang Yong Hu Hainan Liu Ting Gao Qincai Dong Yanwen Jin Ping Li Zijing Liu Yi Huang Xuan Liu Cheng Cao |
| author_facet | Lin Zhu Jing Jin Tingting Wang Yong Hu Hainan Liu Ting Gao Qincai Dong Yanwen Jin Ping Li Zijing Liu Yi Huang Xuan Liu Cheng Cao |
| author_sort | Lin Zhu |
| collection | DOAJ |
| description | Viral inclusion bodies (IBs) commonly form during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK1) or IκB kinase epsilon (IKKε), was recruited and sequestered in viral IBs when the cells were infected by EBOV transcription- and replication-competent virus-like particles (trVLPs). Nucleoprotein/virion protein 35 (VP35)-induced IBs formation was critical for IRF3 recruitment and sequestration, probably through interaction with STING. Consequently, the association of TBK1 and IRF3, which plays a vital role in type I interferon (IFN-I) induction, was blocked by EBOV trVLPs infection. Additionally, IRF3 phosphorylation and nuclear translocation induced by Sendai virus or poly(I:C) stimulation were suppressed by EBOV trVLPs. Furthermore, downregulation of STING significantly attenuated VP35-induced IRF3 accumulation in IBs. Coexpression of the viral proteins by which IB-like structures formed was much more potent in antagonizing IFN-I than expression of the IFN-I antagonist VP35 alone. These results suggested a novel immune evasion mechanism by which EBOV evades host innate immunity. |
| first_indexed | 2024-03-08T09:43:31Z |
| format | Article |
| id | doaj.art-3d9c0c2185cc4c8abbbfa832a8eb3d0e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T09:43:31Z |
| publishDate | 2024-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3d9c0c2185cc4c8abbbfa832a8eb3d0e2024-01-29T16:29:40ZengeLife Sciences Publications LtdeLife2050-084X2024-01-011210.7554/eLife.88122Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunityLin Zhu0https://orcid.org/0000-0001-5772-9482Jing Jin1Tingting Wang2Yong Hu3Hainan Liu4Ting Gao5Qincai Dong6Yanwen Jin7Ping Li8Zijing Liu9Yi Huang10https://orcid.org/0000-0001-6585-5243Xuan Liu11Cheng Cao12Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Physical Science and Information Technology, Anhui University, Hefei, ChinaInstitute of Physical Science and Information Technology, Anhui University, Hefei, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaWuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing, ChinaViral inclusion bodies (IBs) commonly form during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK1) or IκB kinase epsilon (IKKε), was recruited and sequestered in viral IBs when the cells were infected by EBOV transcription- and replication-competent virus-like particles (trVLPs). Nucleoprotein/virion protein 35 (VP35)-induced IBs formation was critical for IRF3 recruitment and sequestration, probably through interaction with STING. Consequently, the association of TBK1 and IRF3, which plays a vital role in type I interferon (IFN-I) induction, was blocked by EBOV trVLPs infection. Additionally, IRF3 phosphorylation and nuclear translocation induced by Sendai virus or poly(I:C) stimulation were suppressed by EBOV trVLPs. Furthermore, downregulation of STING significantly attenuated VP35-induced IRF3 accumulation in IBs. Coexpression of the viral proteins by which IB-like structures formed was much more potent in antagonizing IFN-I than expression of the IFN-I antagonist VP35 alone. These results suggested a novel immune evasion mechanism by which EBOV evades host innate immunity.https://elifesciences.org/articles/88122Ebola virusVP35VP24virus infectionvirus inclusion bodies |
| spellingShingle | Lin Zhu Jing Jin Tingting Wang Yong Hu Hainan Liu Ting Gao Qincai Dong Yanwen Jin Ping Li Zijing Liu Yi Huang Xuan Liu Cheng Cao Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity eLife Ebola virus VP35 VP24 virus infection virus inclusion bodies |
| title | Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity |
| title_full | Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity |
| title_fullStr | Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity |
| title_full_unstemmed | Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity |
| title_short | Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity |
| title_sort | ebola virus sequesters irf3 in viral inclusion bodies to evade host antiviral immunity |
| topic | Ebola virus VP35 VP24 virus infection virus inclusion bodies |
| url | https://elifesciences.org/articles/88122 |
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