A recombinant herpes simplex virus type 1 expressing two additional copies of gK is more pathogenic than wild-type virus in two different strains of mice.
The effect of glycoprotein K (gK) overexpression on herpes simplex virus type 1 (HSV-1) infection in two different strains of mice was evaluated using a recombinant HSV-1 virus that expresses two additional copies of the gK gene in place of the latency-associated transcript (LAT). This mutant virus (HSV-gK3) expressed higher levels of gK than either the wild-type McKrae virus or the parental dLAT2903 virus both in vitro (in cultured cells) and in vivo (in infected mouse corneas and trigeminal ganglia [TG] of BALB/c and C57BL/6 mice). gK transcripts were detected in the TG of both HSV-gK3-infected mouse strains on day 30 postinfection (p.i.), while gB transcripts were detected only in the TG of the HSV-gK3-infected C57BL/6 mice, a finding that suggests that increased gK levels promote chronic infection. C57BL/6 mice infected with HSV-gK3 also contained free virus in their TG on day 30 p.i. Both HSV-gK3-infected mouse strains had significantly higher corneal scarring (CS) than did McKrae-infected mice. T-cell depletion studies in C57BL/6 mice suggested that this CS enhancement in the HSV-gK3-infected mice was mediated by a CD8+ T-cell response. Taken together, these results strongly suggest that increased gK levels promote eye disease and chronic infection in infected mice.
Mott
Kevin R
KR
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, CSMC-D2024, 8700 Beverly Blvd., Los Angeles, California 90048, USA.
Perng
Guey-Chuen
GC
Osorio
Yanira
Y
Kousoulas
Konstantin G
KG
Ghiasi
Homayon
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003315:Cornea / Q000473:pathology; D017353:Gene Deletion; D018628:Gene Dosage; D006566:Herpesviridae Infections; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs; D012668:Trigeminal Ganglion / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D035683:MicroRNAs; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins; D037521:Virulence Factors; C477253:latency associated transcript, herpes simplex virus-1