title: Variability of the glycoprotein G gene in clinical isolates of herpes simplex virus type 1.
abstract: Glycoprotein G (gG) of herpes simplex virus type 1 (HSV-1) has been used as a prototype antigen for HSV-1 type-specific serodiagnosis, but data on the sequence variability of the gene coding for this protein in wild-type strains are lacking. In this study, direct DNA sequencing of the gG-1 genes from PCR products was performed with clinical HSV-1 isolates from 11 subjects as well as with strains Syn 17(+), F, and KOS 321. The reference strains Syn 17(+) and F showed a high degree of conservation, while KOS 321 carried 13 missense mutations and, in addition, 12 silent mutations. Three clinical isolates showed mutations leading to amino acid alterations: one had a mutation of K(122) to N, which is a gG-1-to-gG-2 alteration; another contained all mutations which were observed in KOS 321 except two silent mutations; and the third isolate carried five missense mutations. Two clinical isolates as well as strain KOS 321 showed a mutation (F(111)-->V) within the epitope of a gG-1-reactive monoclonal antibody (MAb). When all viruses were tested for reactivity with the anti-gG-1 MAb, the three strains with the F(111)-->V mutation were found to be unreactive. Furthermore, gG-1 antibodies purified from sera from the two patients carrying strains mutated in this epitope were less reactive when they were tested by an HSV-1-infected-cell assay. Therefore, our finding that the sequence variability of the gG-1 gene also affects B-cell epitope regions of this protein in clinical isolates may have consequences for the use of this protein as a type-specific antigen for serodiagnosis.
authors.affiliation: Department of Clinical Virology, Göteborg University, Göteborg, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Rekabdar
authors.forename: P
authors.initials: P
authors.lastname: Tunbäck
authors.forename: J A
authors.initials: JA
authors.lastname: Liljeqvist
authors.forename: T
authors.initials: T
authors.lastname: Bergström
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D006561:Herpes Simplex / Q000235:genetics* / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000166:cytology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000954:Antigens, Surface; D004279:DNA, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; C050591:glycoprotein gG-1, herpes simplex virus type 1