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. Proposed model showing SNX27 promotes intracellular trafficking of S protein and viral production. (a) SNX27, via its PDZ domain, interacts with S protein and promotes endosome‐to‐plasma membrane trafficking of S protein. SNX27 could also promote the production of SARS‐CoV‐2 virions in host cells, although the mechanism remains poorly defined. (b) Depletion of SNX27 impairs endosome‐to‐plasma membrane trafficking of S protein, leading to its lysosomal degradation.
【저자키워드】 S protein, SARS‐CoV‐2, endosome, endocytic trafficking, host–pathogen interaction, 【초록키워드】 ACE2, Genetic, Infection, Proteins, docking, SARS‐CoV‐2, Protein, pathway, membrane, virus infection, Degradation, RNA virus, expression, Critical, mechanism, binding, host cells, Transport, Factor, domain, Stage, Depletion, SARS‐CoV‐2 infection, receptor ACE2, virion, motif, endosomal trafficking, abrogation, Host, SNX27, approach, decrease, highlight, bind, defined, addition, required, facilitate, interact, promote, impair, lysosomal, endocytic, 【제목키워드】 Spike protein, SARS‐CoV‐2, pathway, endocytic,