Elucidating cellular interactome of chikungunya virus identifies host dependency factors

Peiqi Yin; Xia Jian; Yihan Liu; Yuwen Liu; Lu Lv; Haoran Cui; Leiliang Zhang

doi:10.1016/j.virs.2023.05.007

August 2023

Citation: Peiqi Yin, Xia Jian, Yihan Liu, Yuwen Liu, Lu Lv, Haoran Cui, Leiliang Zhang. Elucidating cellular interactome of chikungunya virus identifies host dependency factors .VIROLOGICA SINICA, 2023, 38(4) : 497-507. http://dx.doi.org/10.1016/j.virs.2023.05.007

Elucidating cellular interactome of chikungunya virus identifies host dependency factors

Peiqi Yin ^a,b ,
Xia Jian ^b ,
Yihan Liu ^c,d ,
Yuwen Liu ^c ,
Lu Lv ^c,d ,
Haoran Cui ^c,d ,
Leiliang Zhang ^{a,c,d
,,}

a. Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250013, China;
b. NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100176, China;
c. Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China;
d. Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China

Corresponding author: Leiliang Zhang, armzhang@hotmail.com
Received Date: 29 November 2022
Accepted Date: 11 May 2023
Available online: 12 May 2023

Abstract

Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain. To better understand how CHIKV rewires the host cell and usurps host cell functions, we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies. One of these novel interactions, between the viral protein E1 and STIP1 homology and U-box containing protein 1 (STUB1), was found to mediate ubiquitination of E1 and degrade E1 through the proteasome. Capsid associated with G3BP1, G3BP2 and AAA+ ATPase valosin-containing protein (VCP). Furthermore, VCP inhibitors blocked CHIKV infection, suggesting VCP could serve as a therapeutic target. Further work is required to fully understand the functional consequences of these interactions. Given that CHIKV proteins are conserved across alphaviruses, many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses. Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.
- Chikungunya virus (CHIKV)
- , Interactome
- , STIP1 homology and U-box containing protein 1 (STUB1)
- , Valosin-containing protein (VCP)
- , Capsid

Electronic Supplementary Material

10.1016j.virs.2023.05.007-ESM1.docx

10.1016j.virs.2023.05.007-ESM2.xls
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