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SARS-CoV-2 spreads through cell-to-cell transmission.
Zeng, Cong; Evans, John P; King, Tiffany; Zheng, Yi-Min; Oltz, Eugene M; Whelan, Sean P J; Saif, Linda J; Peeples, Mark E; Liu, Shan-Lu.
  • Zeng C; Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
  • Evans JP; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • King T; Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
  • Zheng YM; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Oltz EM; Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210.
  • Whelan SPJ; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Saif LJ; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43205.
  • Peeples ME; Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
  • Liu SL; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Article in English | MEDLINE | ID: covidwho-1599544
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / SARS-CoV-2 / COVID-19 Topics: Vaccines / Variants Limits: Animals / Humans Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Internalization / SARS-CoV-2 / COVID-19 Topics: Vaccines / Variants Limits: Animals / Humans Language: English Year: 2022 Document Type: Article