Dr. Cong Zeng and colleagues in their recent study provide evidence that, SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein, which is promoted by cell-cell fusion. Their study recently appeared in bioRxiv.
Viruses can spread in cultured cells and tissues by two fundamentally distinct modes: cell-free or direct cell-cell contact. The latter mode of viral transmission normally involves tight cell-cell contacts, sometimes forming virological synapses, where local viral particle density increases, resulting in efficient transfer of virus to neighbouring cells. Additionally, this transmission has the ability to evade neutralization, accounting for efficient virus spread and pathogenesis, as has been shown for HIV & HCV.
“In this work, we evaluated cell-to-cell transmission of SARS-CoV-2 in the context of cell-free infection and in comparison to SARS-CoV.”— wrote authors of the study
They discovered that SARS-CoV-2 spike is more efficient in mediating cell-to-cell transmission than SARS-CoV spike, yet the spike of SARS-CoV is more capable of mediating cell-free infection.
“To our knowledge, this is the first direct comparison of cell-to-cell transmission vs. cell-free infection between SARS-CoV-2 and SARSCoV in cultured cells, and the results provide important insights into two distinct modes of infection and the host-viral factors that regulate these processes.”— wrote authors of the study
But, why is SARS-CoV-2 spike more efficient than SARS-CoV spike for mediating cell-to-cell transmission in cultured cells? Well, this is in part related to the higher cell-cell fusion activity of SARS-CoV-2 spike compared to SARS-CoV. However, they also recognized that extensive cell-cell fusion by SARS-CoV-2 spike can lead to giant syncytia formation (or you can say black fungus) and cell death, which in turn reduces cell-to-cell transmission. Therefore, fine control of the spike induced cell-cell fusion is important for efficient cell-to-cell transmission and, therefore, the spreading infection of SARS-CoV-2.
In addition, it has been found that, although ACE2 enhances cell-to-cell transmission of SARS-CoV-2 and SARS-CoV, but it is not absolutely required.
Finally, they compared the sensitivity of cell-to-cell transmission vs. cell-free infection of SARS-CoV-2 to treatments by neutralizing monoclonal antibodies and COVID-19 convalescent plasma – both of which have been approved by the FDA for emergency use. They found that while cell-free infection of SARS-CoV-2 was almost completely blocked by these treatments, cell-to-cell transmission of SARS-CoV-2 was, to a large extent, refractory.
“While in this work, we obtained evidence that SARS-CoV-2 spike more efficiently mediates cell-to-cell transmission than the SARS-CoV spike, a direct comparison using authentic viruses of both, especially in primary human lung and airway epithelial cells, is needed. Ultimately, we must determine the role, if any, of cell-to-cell transmission of SARS-CoV-2 in disease progression and pathogenesis in COVID-19 patients.”— concluded authors of the study
Featured image: Schematic representations of cell-to-cell and cell-free infection assays © authors
Reference: Cong Zeng, John P. Evans, Tiffany King, Yi-Min Zheng, Eugene M. Oltz, Sean P. J. Whelan, Linda Saif, Mark E. Peeples, Shan-Lu Liu, “SARS-CoV-2 Spreads through Cell-to-Cell Transmission”, bioRxiv 2021.06.01.446579; doi: https://doi.org/10.1101/2021.06.01.446579
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