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

Autor: Cong Zeng, Evans, John P., King, Tiffany, Yi-Min Zheng, Oltz, Eugene M., Whelan, Sean P. J., Saif, Linda J., Peeples, Mark E., Shan-Lu Liu
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America; 1/4/2022, Vol. 119 Issue 1, p1-12, 12p
Abstrakt: 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 cellto-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 spikemediated cell-to-cell transmission, with important implications for a better understanding of SARS-CoV-2 spread and pathogenesis. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index