Antibody-mediated SARS-CoV-2 entry in cultured cells

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for host cell entry.
• ACE2 engagement induces conformational changes in the viral spike protein, facilitating membrane fusion.

Purpose of the Study:

• To investigate if neutralizing antibodies against SARS-CoV-2 spike protein can substitute for ACE2 in viral entry.
• To explore the mechanisms by which antibodies might mediate viral entry and infectivity.

Main Methods:

• Utilized monoclonal neutralizing antibodies targeting distinct epitopic regions of the SARS-CoV-2 spike protein's receptor-binding domain.
• Tested antibody-mediated viral entry using various antibody formats: soluble IgG-FcγRI complexes, antigen-binding fragment chimeras with ACE2 transmembrane domains, and membrane-bound B cell receptors.
• Assessed membrane fusion and viral infectivity in vitro.

Main Results:

• Monoclonal antibodies targeting specific spike protein epitopes can function as ACE2-independent receptors for SARS-CoV-2.
• Antibody-mediated entry was observed with soluble IgG-FcγRI complexes, ACE2 chimera constructs, and membrane-bound B cell receptors.
• These findings demonstrate that ACE2 interaction is not essential for SARS-CoV-2 entry under certain conditions.

Conclusions:

• Antibodies against SARS-CoV-2 can act as functional receptors, mediating viral entry and infectivity.
• This antibody-driven entry mechanism suggests a potential expansion of viral tropism to non-permissive cells.
• Implications for viral transmission and pathogenesis may arise from antibody-mediated viral spread and altered cell tropism.