Cargando…

A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry

The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma m...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Yunkai, Feng, Fei, Hu, Gaowei, Wang, Yuyan, Yu, Yin, Zhu, Yuanfei, Xu, Wei, Cai, Xia, Sun, Zhiping, Han, Wendong, Ye, Rong, Qu, Di, Ding, Qiang, Huang, Xinxin, Chen, Hongjun, Xie, Youhua, Cai, Qiliang, Yuan, Zhenghong, Zhang, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878750/
https://www.ncbi.nlm.nih.gov/pubmed/33574281
http://dx.doi.org/10.1038/s41467-021-21213-4
Descripción
Sumario:The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.