HSV-1 infection through inhibitory receptor, PILRalpha

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Paired receptors regulate immune responses; viruses often encode ligands for inhibitory receptors to evade immunity.
• Herpes simplex virus type 1 (HSV-1) establishes persistent infections.
• Inhibitory receptors are crucial for immune homeostasis and preventing autoimmunity.

Purpose of the Study:

• To investigate the role of paired immunoglobulin-like receptor alpha (PILRα) in HSV-1 infection.
• To identify HSV-1 components that interact with PILRα.
• To elucidate the mechanism of HSV-1 entry into myeloid cells.

Main Methods:

• Mass spectrometry to identify HSV-1 ligands for PILRα.
• Transfection of PILRα into HSV-1-resistant cells (CHO-K1).
• Analysis of HSV-1 infection in primary human monocytes and lymphocytes.
• Blocking experiments using anti-PILRα and anti-HVEM antibodies/antiserum.

Main Results:

• HSV-1-infected cells express a PILRα ligand.
• HSV-1 glycoprotein B (gB) was identified as a PILRα ligand.
• PILRα expression rendered resistant cells susceptible to HSV-1 infection.
• Monocytes expressing PILRα and HVEM were infected, while lymphocytes lacking PILRα were not.
• Blocking PILRα or HVEM inhibited monocyte infection.

Conclusions:

• HSV-1 utilizes both its gB (binding PILRα) and gD (binding HVEM) to infect cells.
• This study demonstrates, for the first time, viral entry via an inhibitory immune receptor.
• Exploiting inhibitory receptors may facilitate viral entry and immune suppression in hematopoietic cells.