Abstract
SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-bound Angiotensin Converting Enzyme 2. After intracellular assembly, the newly formed virions are released from the infected cells to propagate the infection, using the extra-cytoplasmic ACE2 docking mechanism. However, the molecular events underpinning SARS-CoV-2 transmission between host cells are not fully understood. Here, we report the findings of a scanning Helium-ion microscopy study performed on Vero E6 cells infected with mNeonGreen-expressing SARS-CoV-2. Our data reveal, with unprecedented resolution, the presence of: (1) long tunneling nanotubes that connect two or more host cells over submillimeter distances; (2) large scale multiple cell fusion events (syncytia); and (3) abundant extracellular vesicles of various sizes. Taken together, these ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of viral transmission, disengaged from the well-known extra-cytoplasmic ACE2 docking mechanism. Such route may explain the elusiveness of SARS-CoV-2 to survive from the immune surveillance of the infected host.
Highlights
SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membranebound Angiotensin Converting Enzyme 2
We propose that these three ultrastructural features describe a fully intra-cytoplasmic connection among cells that may act as an alternative route of viral transmission and infection, disengaged from the conventional extra-cytoplasmic angiotensin converting enzyme 2 (ACE2) docking mechanism
These very long filopodia showed the characteristics of Tunneling Nano Tubes (TNT)
Summary
SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membranebound Angiotensin Converting Enzyme 2. With unprecedented resolution, the presence of: (1) long tunneling nanotubes that connect two or more host cells over submillimeter distances; (2) large scale multiple cell fusion events (syncytia); and (3) abundant extracellular vesicles of various sizes Taken together, these ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of viral transmission, disengaged from the well-known extra-cytoplasmic ACE2 docking mechanism. These ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of viral transmission, disengaged from the well-known extra-cytoplasmic ACE2 docking mechanism Such route may explain the elusiveness of SARS-CoV-2 to survive from the immune surveillance of the infected host. Futhermore, the intracytoplasmic viral transmission may explain the ability of SARS-CoV-2 to escape the immune surveillance and the host response
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