Localization of a functional site on herpes simplex virus type 1 glycoprotein C involved in binding to cell surface heparan sulphate.
The amino acid residues critical for interaction between herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) and cell surface heparan sulphate (HS) were localized to two separate regions within antigenic site II of this glycoprotein. These amino acids were Arg-143, Arg-145, Arg-147 and Thr-150 in one region and Gly-247 in the other. This conclusion is based on the following observations. (i) Monoclonal antibodies defining gC-1 antigenic site II, and not those reactive with antigenic site I, inhibited HSV-1-induced haemagglutination and virus binding to susceptible cells. (ii) A number of HSV-1 mar mutants, altered at these critical residues, were impaired in attachment to cells. (iii) Synthetic peptides, corresponding to these two regions inhibited virus attachment to cells and infectivity. In addition these peptides were found to agglutinate red blood cells. This agglutination was inhibited by soluble HS, and was prevented by the pretreatment of red blood cells with heparitinase suggesting that cell surface HS was a site of peptide binding. The same was observed with the polycationic substances neomycin and poly-L-lysine. In conclusion, we propose that the regions of gC-1 represented by the HS-binding peptides may form a functional site of a polycationic nature, active in attachment to the polyanionic glycosaminoglycan chain of cell surface HS.
Trybala
E
E
Department of Clinical Virology, University of Göteborg, Sweden.
Bergström
T
T
Svennerholm
B
B
Jeansson
S
S
Glorioso
J C
JC
Olofsson
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D002460:Cell Line; D000939:Epitopes; D006385:Hemagglutination Inhibition Tests; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D009355:Neomycin / Q000378:metabolism; D009500:Neutralization Tests; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D011107:Polylysine / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D014764:Viral Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D009355:Neomycin; D010455:Peptides; D011107:Polylysine; D011509:Proteoglycans; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C038535:glycoprotein gC, herpes simplex virus type 1