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

Abstract

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.

• Authors: Cong Zeng, John P Evans, Tiffany King, Yi-Min Zheng, Eugene M Oltz, Sean P J Whelan, Linda J Saif, Mark E Peeples, Shan-Lu Liu
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 119 Issue 1 (01 04 2022) ISSN: 1091-6490 [Electronic] United States
• PMID: 34937699 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 the Author(s). Published by PNAS.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2
• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral
• COVID-19 (immunology, therapy, transmission)
• Cell Fusion
• Chlorocebus aethiops
• HEK293 Cells
• Humans
• Immunization, Passive
• SARS-CoV-2 (immunology)
• Spike Glycoprotein, Coronavirus (immunology)
• Vero Cells
• Virus Internalization
• COVID-19 Serotherapy