title: Strain-dependent structural variants of herpes simplex virus type 1 ICP34.5 determine viral plaque size, efficiency of glycoprotein processing, and viral release and neuroinvasive disease potential.
abstract: The ability of certain strains of herpes simplex virus type 1 (HSV-1) to cause encephalitis or neuroinvasive disease in the mouse upon peripheral infection is dependent on a combination of activities of specific forms of viral proteins. The importance of specific variants of ICP34.5 to neuroinvasive disease potential and its correlation with small-plaque production, inefficient glycoprotein processing, and virus release were suggested by comparison of ICP34.5 from the SP7 virus, originally obtained from the brain of a neonate with disseminated disease, and the tissue culture-passaged progeny of SP7 (SLP5 and SLP10) and the KOS321 virus. SLP5, SLP10, and KOS321 are attenuated and exhibit a large-plaque phenotype, including efficient glycoprotein processing and viral release. We show that expression of the KOS321 ICP34.5 protein in cells infected with SP7 or ICP34.5 deletion mutants promotes large plaque formation and efficient viral glycoprotein processing, while expression of the SP7 ICP34.5 protein decreases efficiency of viral glycoprotein processing. In addition, a recombinant virus, 4hS1, with the SP7 ICP34.5 gene replacing the KOS321-like ICP34.5 gene in the SLP10a background, rescues the small-plaque phenotype and neuroinvasive disease. The major difference in the ICP34.5 gene product is the number of Pro-Ala-Thr repeats in the middle region of the protein, with 18 for SP7 and 3 for KOS321. Strain-dependent differences in the ICP34.5 protein can therefore alter the tissue culture behavior and the virulence of HSV-1.
authors.affiliation: Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Mao
authors.forename: Ken S
authors.initials: KS
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D020803:Encephalitis, Herpes Simplex / Q000503:physiopathology* / Q000821:virology; D014644:Genetic Variation; D018259:Herpesvirus 1, Human / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D014759:Viral Envelope Proteins; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; C038535:glycoprotein gC, herpes simplex virus type 1