Journal Article

SARS-CoV-2 spreads through cell-to-cell transmission

Evans, John P., Zeng, Cong, Whelan, Sean P. J., Liu, Shan-Lu, King, Tiffany, Saif, Linda J., Peeples, Mark E., Oltz, Eugene M., Zheng, Yi-Min

2022

Overview

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell–cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell–cell fusion activity. Interestingly, treatment of cocultured cells with endosomal entry inhibitors impairs cell-to-cell transmission, implicating endosomal membrane fusion as an underlying mechanism. Compared with cell-free infection, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. While angiotensin-converting enzyme 2 enhances cell-to-cell transmission, we find that it is not absolutely required. Notably, despite differences in cell-free infectivity, the authentic variants of concern (VOCs) B.1.1.7 (alpha) and B.1.351 (beta) have similar cell-to-cell transmission capability. Moreover, B.1.351 is more resistant to neutralization by vaccinee sera in cell-free infection, whereas B.1.1.7 is more resistant to inhibition by vaccinee sera in cell-to-cell transmission. Overall, our study reveals critical features of SARS-CoV-2 spike-mediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis.

• Publisher: National Academy of Sciences
• Subject: ACE2 / Angiotensin / Angiotensin-Converting Enzyme 2 / Animals / Antibodies / Antibodies, Neutralizing - immunology / Antibodies, Viral / Biological Sciences / Cell Fusion / Chlorocebus aethiops / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - therapy / COVID-19 - transmission / Disease transmission / Glycoproteins / HEK293 Cells / Humans / Immunization, Passive / Infectivity / Membrane fusion / Microbiology / Neutralization / Pandemics / Pathogenesis / Peptidyl-dipeptidase A / Respiratory diseases / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Spike glycoprotein / Spike Glycoprotein, Coronavirus - immunology / Vero Cells / Viral diseases / Virus Internalization