PMID:11602758

Citation	Martinez, WM and Spear, PG (2001) Structural features of nectin-2 (HveB) required for herpes simplex virus entry. J. Virol. 75:11185-95
Abstract	One step in the process of herpes simplex virus (HSV) entry into cells is the binding of viral glycoprotein D (gD) to a cellular receptor. Human nectin-2 (also known as HveB and Prr2), a member of the immunoglobulin (Ig) superfamily, serves as a gD receptor for the entry of HSV-2, variant forms of HSV-1 that have amino acid substitutions at position 25 or 27 of gD (for example, HSV-1/Rid), and porcine pseudorabies virus (PRV). The gD binding region of nectin-2 is believed to be localized to the N-terminal variable-like (V) Ig domain. In order to identify specific amino acid sequences in nectin-2 that are important for HSV entry activity, chimeric molecules were constructed by exchange of sequences between human nectin-2 and its mouse homolog, mouse nectin-2, which mediates entry of PRV but not HSV-1 or HSV-2. The nectin-2 chimeric molecules were expressed in Chinese hamster ovary cells, which normally lack a gD receptor, and tested for cell surface expression and viral entry activity. As expected, chimeric molecules containing the V domain of human nectin-2 exhibited HSV entry activity. Replacement of either of two small regions in the V domain of mouse nectin-2 with amino acids from the equivalent positions in human nectin-2 (amino acids 75 to 81 or 89) transferred HSV-1/Rid entry activity to mouse nectin-2. The resulting chimeras also exhibited enhanced HSV-2 entry activity and gained the ability to mediate wild-type HSV-1 entry. Replacement of amino acid 89 of human nectin-2 with the corresponding mouse amino acid (M89F) eliminated HSV entry activity. These results identify two different amino acid sequences, predicted to lie adjacent to the C' and C" beta-strands of the V domain, that are critical for HSV entry activity. This region is homologous to the human immunodeficiency virus binding region of CD4 and to the poliovirus binding region of CD155.
Links	PubMed PMC114698 Online version:10.1128/JVI.75.22.11185-11195.2001
Keywords	Amino Acid Sequence; Animals; Cell Adhesion Molecules/chemistry; Cell Adhesion Molecules/physiology; Humans; Mice; Molecular Sequence Data; Receptors, Virus/chemistry; Receptors, Virus/physiology; Simplexvirus/physiology; Species Specificity; Structure-Activity Relationship
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:NECT2		GO:0046596: regulation of viral entry into host cell	ECO:0000314:		P		Fig. 2. Cells were transfected with the protein to determine ease of viral entry	complete CACAO 6560
HUMAN:NECT2	involved_in	GO:0046596: regulation of viral entry into host cell	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

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