LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2

Area of Science:

• Virology
• Immunology

Background:

• Virus entry into host cells determines host range and tropism.
• Innate and adaptive immune responses control viral entry.
• Several interferon-inducible proteins modulate viral entry.

Purpose of the Study:

• Investigate host cellular proteins mediating differential susceptibility to HCoV-OC43 infection.
• Identify host factors controlling coronavirus entry and pathogenesis.

Main Methods:

• Compared HCoV-OC43 susceptibility between HepG2 and C3A cell lines.
• Analyzed expression of ADAP2, GILT, and LY6E.
• Performed functional analyses of LY6E, GILT, and ADAP2 in HEK 293, C3A, and A549 cells.
• Knocked down LY6E expression in HepG2 cells.

Main Results:

• C3A cells showed higher susceptibility to HCoV-OC43 than HepG2 cells due to increased virus entry efficiency.
• LY6E, but not GILT or ADAP2, inhibited HCoV-OC43 entry when ectopically expressed.
• Overexpression of LY6E inhibited HCoV-OC43 infection in C3A and A549 cells.
• LY6E knockdown in HepG2 cells increased HCoV-OC43 susceptibility.
• LY6E restricted entry mediated by spike proteins of other human coronaviruses, including SARS-CoV-2.
• LY6E's antiviral effect was distinct from TMPRSS2, amphotericin, and IFITM3.

Conclusions:

• LY6E is a critical antiviral immune effector controlling coronavirus infection and pathogenesis.
• LY6E restricts coronavirus entry through a mechanism distinct from other known factors.
• LY6E's role as a coronavirus restriction factor expands its known biological functions.