Author
Listed:
- Shiyu Dai
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
Soochow University)
- Yuan-Qin Min
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences)
- Qi Li
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
University of Chinese Academy of Sciences)
- Kuan Feng
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences)
- Zhenyu Jiang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
University of Chinese Academy of Sciences)
- Zhiying Wang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences)
- Cunhuan Zhang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences)
- Fuli Ren
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences)
- Yaohui Fang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
University of Chinese Academy of Sciences)
- Jingyuan Zhang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
University of Chinese Academy of Sciences)
- Qiong Zhu
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences)
- Manli Wang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences)
- Hualin Wang
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences)
- Fei Deng
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences)
- Yun-Jia Ning
(Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences
State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences
Hubei Jiangxia Laboratory)
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.
Suggested Citation
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, 2023.
"Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
Handle:
RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43206-1
DOI: 10.1038/s41467-023-43206-1
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