title: Novel deletion in glycoprotein G forms a cluster and causes epidemiologic spread of herpes simplex virus type 2 infection.
abstract: The herpes simplex virus type 2 (HSV-2) glycoprotein G (gG-2) gene of 106 clinical isolates was analyzed and six isolates were identified with 63 nucleotides comprising 21 amino acids (aa) deleted in the immunodominant region. Compared with strain HG52, variations in the gG-2 gene were found at 276 and 27 sites in nucleotide and aa sequences, respectively, in the 106 strains. Significant variations in both nucleotides and aa were accumulated in the immunodominant region rather than in the other regions (P < 0.001), indicating that the immunodominant region might be indispensable in vivo and a hot spot for variation. The frequency of 21 aa-deleted strains (HSVΔ21/gG-2) among clinical isolates was 5%, indicating the advantage of this deletion of gG-2 for epidemiological expansion. Phylogenetic analysis of the 106 strains indicated that the HSVΔ21/gG-2 strains formed a cluster among the various variations but that their genomes showed different endonuclease digestion patterns. The antibody titers to total HSV antigens of patients infected with wild HSV-2 and HSVΔ21/gG-2 were similar, but patients with HSVΔ21/gG-2 had a lower antibody titer to gG-2 than those with wild HSV-2 (P < 0.001). HSVΔ21/gG-2 might be less immnunogenic and reduce antibody production to gG-2, while its pathogenicity in humans was not distinguished in its clinical manifestations. Thus, infection with HSVΔ21/gG-2 caused genital lesions similar to wild HSV-2 infection, but evaded the immune response to gG-2 to allow epidemiological spread, indicating the importance of this deletion in the immunodominant region of gG-2 in the pathogenesis and transmission of genital herpes.
authors.affiliation: Department of Virology, University of Toyama, Toyama, Japan. tdaikoku@med.u-toyama.ac.jp
authors.forename: Tohru
authors.initials: T
authors.lastname: Daikoku
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Horiba
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawana
authors.forename: Masaru
authors.initials: M
authors.lastname: Hirano
authors.forename: Kimiyasu
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D016000:Cluster Analysis; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006558:Herpes Genitalis / Q000453:epidemiology* / Q000276:immunology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000145:classification* / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D057131:Immune Evasion; D016056:Immunodominant Epitopes / Q000235:genetics; D017720:Molecular Epidemiology; D010802:Phylogeny; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins; C045464:glycoprotein G, herpes simplex virus type 2
keywords: HSV-2; genital herpes; glycoprotein G; immune evasion immune evasion