Epidermal growth factor receptor is a cellular receptor for human cytomegalovirus

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Human cytomegalovirus (HCMV) is a prevalent opportunistic herpesvirus with severe health implications for immunocompromised individuals and a leading cause of congenital defects.
• HCMV infection involves receptor binding and activation of cellular signaling pathways, but the specific cellular receptor for viral entry and signaling has remained elusive.
• Previous research identified signaling pathways like MAPK and PI3K activated by HCMV, but the initial interaction point was unknown.

Purpose of the Study:

• To identify the cellular receptor mediating HCMV entry and subsequent intracellular signaling.
• To elucidate the role of specific cellular receptors in HCMV pathogenesis and infection.

Main Methods:

• Utilized EGFR-negative cells and EGFR-complementary DNA transfection to assess cellular susceptibility to HCMV.
• Employed ligand displacement and crosslinking analyses to investigate the interaction between HCMV and EGFR.
• Examined the binding preferences of HCMV glycoprotein gB to EGFR and ErbB family members in transfected cells.

Main Results:

• Demonstrated that HCMV infection and signaling are dependent on the epidermal growth factor receptor (EGFR).
• Showed that EGFR-negative cells become susceptible to HCMV upon EGFR transfection.
• Confirmed HCMV interacts with EGFR via its envelope glycoprotein gB, with a preference for EGFR and EGFR-ErbB3 complexes.

Conclusions:

• Epidermal growth factor receptor (EGFR) is a crucial cellular component for HCMV-triggered signaling and viral entry.
• The interaction between HCMV's gB and EGFR is essential for initiating infection.
• This finding provides a novel target for understanding and potentially combating HCMV infections.