Herpes simplex virus 1 (HSV-1) strain HSZP glycoprotein B gene: comparison of mutations among strains differing in virulence.
The nonpathogenic HSZP strain of HSV-1 induces large polykaryocytes due to a syn3 mutation (His for Arg at residue 858) in the C-terminal endodomain of glycoprotein B (gB) (40). We determined the nucleotide (nt) sequence of the UL27 gene specifying the gB polypeptide of HSZP (gBHSZP) and found 3 mutations in its ectodomain at aminoacids (aa) 59, 79 and 108. The ANGpath virus, which also has a syn3 mutation in the C-terminal endodomain of gB (Val for Ala at residue 855) is pathogenic for adult mice (39), but can be made nonpathogenic by replacing the gBANGpath gene by the corresponding gBKOS sequence (21). The gBANGpath had three ectodomain mutations (at aa 62, 77 and 285), while gBKOS had at least four ectomain mutations (aa 59, 79, 313, and 553). Two mutations (aa 59 and 79) in the latter, located in the variable antigenic site IV/D1 were common for gBKOS and gBHSZP. These together with the gBANGpath mutations at aa 62 and 77 create a cluster of 4 mutations in diverse region of the N-terminal part of gB (between aa 59-79), in which the gBs of pathogenic ANGpath and 17 viruses differ from the gBs of nonpathogenic HSZP and KOS viruses. The lower pathogenicity of KOS as related to gBKOS, is furthermore associated with the change of Ser to Thr at aa 313 (locus III/D2). The possibility is discussed that mutations in both above mentioned antigenic loci could result in higher immunogenicity of the corresponding antigenic epitopes, which, in turn, would contribute to the decreased virulence of HSZP and KOS viruses.
Kosovský
J
J
Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Vojvodová
A
A
Oravcová
I
I
Kúdelová
M
M
Matis
J
J
Rajcáni
J
J
D019943:Amino Acid Substitution; D000818:Animals; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D011817:Rabbits; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence
D004279:DNA, Viral; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus