tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 Jan 4;119(1):e2111400119.
doi: 10.1073/pnas.2111400119.
SARS-CoV-2 spreads through cell-to-cell transmission
Cong Zeng[SUP] 1 2 [/SUP], John P Evans[SUP] 1 2 3 [/SUP], Tiffany King[SUP] 4 5 [/SUP], Yi-Min Zheng[SUP] 1 2 [/SUP], Eugene M Oltz[SUP] 6 [/SUP], Sean P J Whelan[SUP] 7 [/SUP], Linda J Saif[SUP] 8 9 10 [/SUP], Mark E Peeples[SUP] 4 5 10 [/SUP], Shan-Lu Liu[SUP] 11 2 6 10 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; cell-to-cell transmission; cell–cell fusion; neutralization; variants of concern.
. 2022 Jan 4;119(1):e2111400119.
doi: 10.1073/pnas.2111400119.
SARS-CoV-2 spreads through cell-to-cell transmission
Cong Zeng[SUP] 1 2 [/SUP], John P Evans[SUP] 1 2 3 [/SUP], Tiffany King[SUP] 4 5 [/SUP], Yi-Min Zheng[SUP] 1 2 [/SUP], Eugene M Oltz[SUP] 6 [/SUP], Sean P J Whelan[SUP] 7 [/SUP], Linda J Saif[SUP] 8 9 10 [/SUP], Mark E Peeples[SUP] 4 5 10 [/SUP], Shan-Lu Liu[SUP] 11 2 6 10 [/SUP]
Affiliations
- PMID: 34937699
- DOI: 10.1073/pnas.2111400119
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.
Keywords: SARS-CoV-2; cell-to-cell transmission; cell–cell fusion; neutralization; variants of concern.