title: Critical residues in the CC' ridge of the human nectin1 receptor V domain enable herpes simplex virus entry into the cell and act synergistically with the downstream region.
abstract: The site on nectin1 receptor required for herpes simplex virus (HSV) entry into the cell was previously mapped to the 64-94 region, encompassing the predicted CC'C" region of the immunoglobulin V domain. Within it lies a minimal HSV entry site (residues 77-94). Here we transferred the 65-76 region (C strand and CC' loop) and portions, or single amino acids, thereof to nectin2, a homolog nonfunctional for wt HSV-1 entry. Replacement of the seven- or of three-amino-acid-long stretches from nectin1 to nectin2 (amino acids 69-75, 69-71, or 72-75) transferred wt HSV-1 and BHV-1 entry activity and enhanced HSV-2, PrV, and HSV-HSV(U21) entry to levels observed with nectin1. Thus, the CC' ridge is sufficient to mediate wt HSV entry at a reduced level and responsible for the wide virus range of the receptor. Altogether the HSV entry site appears to be composed of contiguous synergistic regions, 64-76 and 77-94, each independently capable of mediating virus entry at reduced efficiency.
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D000075983:Nectins; D011991:Receptors, Virus / Q000737:chemistry* / Q000502:physiology; D018139:Simplexvirus / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D011991:Receptors, Virus