title: Nucleotide sequences important in DNA replication are responsible for differences in the capacity of two herpes simplex virus strains to spread from cornea to central nervous system.
abstract: Two herpes simplex virus (HSV) intertypic recombinants were isolated with genomes composed entirely of HSV-2(186) nucleotide sequences except for a 6.0 kb segment of HSV-1(17) DNA positioned between 0.40 and 0.44 map units. Following corneal infection of mice, HSV-1(17) and the two intertypic recombinants spread from infected eyes into the central nervous system and induced a fatal encephalitis. Ocular infection with the HSV-2(186) parent did not lead to detectable amounts of virus in the brain, and none of the mice developed encephalitis. The 6.0 kb HSV-1(17) DNA inserted within the genome of the two intertypic recombinants contained nucleotide sequences involved in DNA replication. These include the HSV-1(17) oriL, the HSV-1(17) gene for DNA polymerase and portions of the HSV-1(17) gene coding for DNA-binding protein ICP8. Thus, our results indicate that the difference in the capacity of HSV-1(17) and HSV-2(186) to spread from the cornea into the CNS is determined solely by nucleotide sequences associated with DNA replication.
mesh_terms: D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000382:microbiology*; D002999:Clone Cells; D003315:Cornea / Q000382:microbiology*; D003433:Crosses, Genetic; D003434:Crossing Over, Genetic; D004261:DNA Replication; D004274:DNA, Recombinant / Q000502:physiology; D004279:DNA, Viral / Q000502:physiology; D005724:Ganglia / Q000382:microbiology; D005814:Genes, Viral; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D014276:Trigeminal Nerve / Q000382:microbiology; D014774:Virulence
chemical_list: D004274:DNA, Recombinant; D004279:DNA, Viral