SARS‐CoV‐2 spike protein harnesses SNX27‐mediated endocytic recycling pathway
Lin Zhao,
Kunhong Zhong,
Jia Zhao,
Xin Yong,
Aiping Tong,
Da Jia
Affiliations
Lin Zhao
Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of Paediatrics State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy West China Second University Hospital Sichuan University Chengdu China
Kunhong Zhong
State Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University Chengdu China
Jia Zhao
Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of Paediatrics State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy West China Second University Hospital Sichuan University Chengdu China
Xin Yong
Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of Paediatrics State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy West China Second University Hospital Sichuan University Chengdu China
Aiping Tong
State Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University Chengdu China
Da Jia
Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of Paediatrics State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy West China Second University Hospital Sichuan University Chengdu China
Abstract SARS‐CoV‐2 is an enveloped positive‐sense RNA virus that depends on host factors for all stages of its life. Membrane receptor ACE2 is a well‐established factor for SARS‐CoV‐2 docking. In addition to ACE2, whole‐genome genetic screens have identified additional proteins, such as endosomal trafficking regulators SNX27 and retromer, as key host factors required for SARS‐CoV‐2 infection. However, it is poorly understood how SARS‐CoV‐2 utilize host endocytic transport pathways to produce productive infection. Here, we report that SNX27 interacts with the SARS‐CoV‐2 spike (S) protein to facilitate S protein surface expression. Interestingly, S protein binds to the PDZ domain of SNX27, although it does not contain a PDZ‐binding motif (PDZbm). Either abrogation of the SNX27 PDZ domain or S protein “MTSC” motif, which is critical for SNX27 binding, decreases surface expression of S protein and viral production. Collectively, our study highlights a novel approach utilized by SARS‐CoV‐2 to facilitate virion trafficking to establish virus infection.
