DMV biogenesis during beta-coronavirus infection requires autophagy proteins VMP1 and TMEM41B

Ji, Mingming1; Li, Meng2; Sun, Long3,4; Deng, Hongyu3,4; Zhao, Yan G.2,5

2022-07-01

10.1080/15548627.2022.2103783

Autophagy   Impact Factor & Quartile

1554-8627

1554-8635

Upon entering host cells, beta-coronaviruses specifically induce generation of replication organelles (ROs) from the endoplasmic reticulum (ER) through their nonstructural protein 3 (nsp3) and nsp4 for viral genome transcription and replication. The most predominant ROs are double-membrane vesicles (DMVs). The ER-resident proteins VMP1 and TMEM41B, which form a complex to regulate autophagosome and lipid droplet (LD) formation, were recently shown to be essential for beta-coronavirus infection. Here we report that VMP1 and TMEM41B contribute to DMV generation but function at different steps. TMEM41B facilitates nsp3-nsp4 interaction and ER zippering, while VMP1 is required for subsequent closing of the paired ER into DMVs. Additionally, inhibition of phosphatidylserine (PS) formation by siPTDSS1 partially reverses the DMV and LD defects in VMP1 KO cells, suggesting that appropriate PS levels also contribute to DMV formation. This work provides clues to the mechanism of how host proteins collaborate with viral proteins for endomembrane reshaping to promote viral infection.

Beta-coronavirus DMV nsp3 nsp4 TMEM41B VMP1

SCI

English

Corresponding

Chinese Ministry of Science and Technology of the People's Republic of China [National Key Research and Development Program][2021YFA1300802] ; National Natural Science Foundation of China (NSFC)[32170753] ; Chinese Academy of Sciences["XDB37030205","KJZD-SW-L05"] ; ShenzhenHong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions[2022SHIBS0002]

Cell Biology

Cell Biology

WOS:000832517900001

TAYLOR & FRANCIS INC

Web of Science

1.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China
2.Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China
3.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, CAS Key Lab Infect & Immun, Beijing 100101, Peoples R China
4.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
5.Southern Univ Sci & Technol, Brain Res Ctr, Sch Life Sci, Dept Biol, Shenzhen, Guangdong, Peoples R China

Ji, Mingming,Li, Meng,Sun, Long,et al. DMV biogenesis during beta-coronavirus infection requires autophagy proteins VMP1 and TMEM41B[J]. Autophagy,2022.

Ji, Mingming,Li, Meng,Sun, Long,Deng, Hongyu,&Zhao, Yan G..(2022).DMV biogenesis during beta-coronavirus infection requires autophagy proteins VMP1 and TMEM41B.Autophagy.

Ji, Mingming,et al."DMV biogenesis during beta-coronavirus infection requires autophagy proteins VMP1 and TMEM41B".Autophagy (2022).