title: Cellular receptor structures for pseudorabies virus are blocked by antithrombin III.
abstract: Pseudorabies virus (PrV), an alphaherpesvirus of swine, uses cellular heparan sulfate residues as a receptor for attachment. Interaction of the virus with its receptor is mediated by the envelope glycoprotein C (PrV-gC), a protein with heparin-binding properties. We have previously shown that a region of this protein shows structural similarities to the high-affinity heparin-binding site of the serum protease-inhibitor antithrombin III (ATII). In this publication, we describe the effect of ATIII on interaction of PrV with its cellular receptor. ATIII bound specifically to heparan sulfate residues on the surface of herpesvirus-permissive RK13 cells. Binding of ATIII to RK13 cells interfered with adsorption of radioactively labelled PrV to these cells. Enzymatic treatment using heparinase I (E.C. 4.2.2.7) removed the receptor for PrV as well as the receptor for ATIII. Since amino acids 130-137 of the high affinity heparin-binding site of ATIII show structural similarities to amino acids 134-141 of PrV-gC, both sequences were synthesized as synthetic peptides. Although interaction of the peptide derived from ATIII with heparin was significantly stronger, both peptides interacted specifically with heparin in assays in vitro. These results suggest that PrV and ATIII interact with the same structure on the cellular surface.
authors.affiliation: Institute for Clinical and Experimental Virology, Free University Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Voigt
authors.forename: D
authors.initials: D
authors.lastname: Sawitzky
authors.forename: H
authors.initials: H
authors.lastname: Zeichhardt
authors.forename: K O
authors.initials: KO
authors.lastname: Habermehl
mesh_terms: D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D006493:Heparin / Q000378:metabolism; D011558:Herpesvirus 1, Suid / Q000502:physiology*; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: D011991:Receptors, Virus; D000990:Antithrombin III; D006493:Heparin