Open AccessSARS‐CoV‐2 spike protein harnesses SNX27‐mediated endocytic recycling pathway
Author(s) -
Zhao Lin,
Zhong Kunhong,
Zhao Jia,
Yong Xin,
Tong Aiping,
Jia Da
Publication year - 2021
Publication title -
medcomm
Language(s) - English
Resource type - Journals
ISSN - 2688-2663
DOI - 10.1002/mco2.92
Subject(s) - pdz domain , endocytic cycle , endosome , retromer , microbiology and biotechnology , biology , sorting nexin , viral entry , viral protein , transport protein , virus , virology , genetics , receptor , viral replication , endocytosis , intracellular
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.