[Cell entry mechanisms of coronaviruses]

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Enveloped viruses, including coronaviruses (CoVs), depend on their Spike (S) protein for cellular entry.
• Understanding CoV cell entry mechanisms is crucial for comprehending viral pathogenesis and disease severity.

Purpose of the Study:

• To investigate and compare the cell entry mechanisms of two distinct CoVs: murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV).
• To elucidate the role of the Spike (S) protein and proteases in CoV cell entry pathways.

Main Methods:

• Comparative analysis of cell entry mechanisms for MHV and SARS-CoV strains.
• Investigation of syncytia formation as an indicator of cell entry pathway.
• Assessment of protease-dependent fusion activity and receptor-binding interactions.

Main Results:

• MHV-JHM, which induces syncytia, enters cells via direct fusion at the cell surface.
• SARS-CoV and MHV-2, which do not induce syncytia, enter via endosomal fusion in a protease-dependent manner.
• Protease treatment activates fusion activity of SARS-CoV and MHV-2 S proteins, enabling direct cell surface entry.
• Highly neurovirulent MHV-JHM exhibits receptor-independent spread, correlating with high neuropathogenicity.

Conclusions:

• CoV cell entry pathways are diverse, involving either direct cell surface fusion or endosomal fusion.
• The entry route of SARS-CoV may impact disease severity.
• Receptor-independent spread of neurovirulent CoVs contributes to their neuropathogenicity.