Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins
Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43206-1 |
| _version_ | 1827710288799989760 |
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| author | Shiyu Dai Yuan-Qin Min Qi Li Kuan Feng Zhenyu Jiang Zhiying Wang Cunhuan Zhang Fuli Ren Yaohui Fang Jingyuan Zhang Qiong Zhu Manli Wang Hualin Wang Fei Deng Yun-Jia Ning |
| author_facet | Shiyu Dai Yuan-Qin Min Qi Li Kuan Feng Zhenyu Jiang Zhiying Wang Cunhuan Zhang Fuli Ren Yaohui Fang Jingyuan Zhang Qiong Zhu Manli Wang Hualin Wang Fei Deng Yun-Jia Ning |
| author_sort | Shiyu Dai |
| collection | DOAJ |
| description | Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches. |
| first_indexed | 2024-03-10T17:36:00Z |
| format | Article |
| id | doaj.art-d8695d1c7b9b4628962672891048d421 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:36:00Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d8695d1c7b9b4628962672891048d4212023-11-20T09:52:51ZengNature PortfolioNature Communications2041-17232023-11-0114111810.1038/s41467-023-43206-1Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteinsShiyu Dai0Yuan-Qin Min1Qi Li2Kuan Feng3Zhenyu Jiang4Zhiying Wang5Cunhuan Zhang6Fuli Ren7Yaohui Fang8Jingyuan Zhang9Qiong Zhu10Manli Wang11Hualin Wang12Fei Deng13Yun-Jia Ning14Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesKey Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of SciencesAbstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 pathogen requiring urgent research and development efforts. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in multiple cellular biological processes potentially associated with the physiological actions of the viral glycoproteins. Then, we elucidated the role of a representative cellular protein, HAX1. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is required for functional glycoprotein-mediated progeny virion packaging. Consistently, the inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections in cellular and animal models. Together, the findings provide a systematic CCHFV Gn/Gc-cell protein-protein interaction map, but also unravel a HAX1/mitochondrion-associated host antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.https://doi.org/10.1038/s41467-023-43206-1 |
| spellingShingle | Shiyu Dai Yuan-Qin Min Qi Li Kuan Feng Zhenyu Jiang Zhiying Wang Cunhuan Zhang Fuli Ren Yaohui Fang Jingyuan Zhang Qiong Zhu Manli Wang Hualin Wang Fei Deng Yun-Jia Ning Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins Nature Communications |
| title | Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins |
| title_full | Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins |
| title_fullStr | Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins |
| title_full_unstemmed | Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins |
| title_short | Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins |
| title_sort | interactome profiling of crimean congo hemorrhagic fever virus glycoproteins |
| url | https://doi.org/10.1038/s41467-023-43206-1 |
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