2. Academic Validation
  3. Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins

Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins

  • Nat Commun. 2023 Nov 14;14(1):7365. doi: 10.1038/s41467-023-43206-1.
Shiyu Dai # 1 2,  Yuan-Qin Min # 1 3,  Qi Li 1 4,  Kuan Feng 1 3,  Zhenyu Jiang 1 4,  Zhiying Wang 1,  Cunhuan Zhang 1,  Fuli Ren 1,  Yaohui Fang 1 4,  Jingyuan Zhang 1 4,  Qiong Zhu 1 3,  Manli Wang 1 3,  Hualin Wang 5 6,  Fei Deng 7 8,  Yun-Jia Ning 9 10 11
Affiliations

Affiliations

  • 1 Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China.
  • 2 Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, 215006, China.
  • 3 State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China.
  • 4 University of Chinese Academy of Sciences, 101408, Beijing, China.
  • 5 Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China. h.wang@wh.iov.cn.
  • 6 State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China. h.wang@wh.iov.cn.
  • 7 Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China. df@wh.iov.cn.
  • 8 State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China. df@wh.iov.cn.
  • 9 Key Laboratory of Virology and Biosafety and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China. nyj@wh.iov.cn.
  • 10 State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China. nyj@wh.iov.cn.
  • 11 Hubei Jiangxia Laboratory, Wuhan, 430200, China. nyj@wh.iov.cn.
  • # Contributed equally.
PMID: 37963884 DOI: 10.1038/s41467-023-43206-1
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.

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