Evidence endogenous interferon production contributed to the lack of ocular virulence of an HSV intertypic recombinant.
An intertypic recombinant isolated from rabbit kidney cells following co-transfection of HSV-1(17) and HSV-2(186) DNA failed to induce overt ocular pathology when inoculated onto the murine sacrificed cornea at concentrations as high as 10(7) PFU per eye. In contrast, both parents induced corneal disease at a 1000-fold lower dose. The reason(s) for the failure of the intertypic recombinant, designated RO25X, to induce corneal pathology was investigated. It was found that the recombinant was 100-fold more sensitive to the inhibitory effects of interferon (IFN) alpha/beta than the parent strains in corneal button growth studies in vitro. R025X readily grew in cultured mouse corneal fibroblasts at a low multiplicity of infection. However, the peak titer was approximately 8-fold lower than that of strain 17. Addition of rabbit anti-IFN alpha/beta to the culture medium resulted in a 4 to 5-fold increase in infectious titer compared to its growth in the absence of antiserum. Most significantly, when mice were pre-treated in vivo with anti-IFN alpha/beta 24 hours prior to virus corneal infection, 67% of the recipients developed moderate to severe stromal keratitis, whereas none of the controls developed corneal pathology. Blepharitis was also significantly increased in incidence and severity in the antiserum treated hosts. We conclude that the inability of R025X to induce ocular disease was due, at least in part, to the inhibitory effects of interferon produced in response to infection.
Lausch
R N
RN
University of South Alabama, College of Medicine, Department of Microbiology and Immunology, Mobile 36688.
Su
Y H
YH
Ritchie
M
M
Oakes
J E
JE
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003315:Cornea / Q000382:microbiology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000382:microbiology; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology*; D007635:Keratitis, Dendritic / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity*; D014162:Transfection / Q000235:genetics; D014774:Virulence / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D007370:Interferon Type I