Infrastructure Interdependencies and Homeland Security

Abstract

Paired immunoglobulin-like type 2 receptor alpha (PILR{alpha}) and beta (PILR{beta}) are paired receptors that are highly homologous to each other. When engaged by ligand, PILR{alpha} is inhibitory whereas PILR{beta} is activating. PILR{alpha} is a newly identified herpes simplex virus 1 (HSV-1) glycoprotein B (gB) receptor and is associated with membrane fusion and entry activity of HSV-1. PILR{alpha} is a 303 amino acid protein with an immunoglobulin (Ig)-like V (variable)-type domain from amino acids 31 to 150, whereas PILR{beta} is a 217 amino acid protein with an Ig-like V-type domain from amino acids 21 to 143. We report that PILR{beta} is not a receptor for HSV-1 and HSV-2. Domain swaps between PILR{alpha} and PILR{beta} reveal the Ig-like V-type domain of PILR{alpha}, but not PILR{beta}, plays a critical role in cell membrane fusion activity and the binding of PILR{alpha} to gB. Individual substitution of thirteen amino acids in PILR{alpha} showed that most of these mutations had no effect on cell fusion activity. However, mutation of the tryptophan residue at amino acid 139 significantly impaired cell fusion activity for HSV-1 and eliminated binding to gB.