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Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA
Abstract:
The pattern of ocular disease produced in the rabbit eye by HSV-1 (F) and HSV-1(MP) strains and recombinants F(MP)A, F(MP)B, F(MP)C, F(MP)D, F(MP)E, and F(MP)F was studied. The characteristics of ocular herpetic disease such as morphology of dendritic ulcers, severity of epithelial disease and incidence and duration of stromal disease produced in the rabbit eye are genetically determined by the virus strain. Our studies show that transfer of a defined part of the genome of the stromal disease-producing virus, HSV-1(MP), to the genome of an epithelial disease-producing virus, HSV-1(F), yielded recombinants with one or more of the disease characteristics of the donor strain. Specifically, recombinant F(MP)D produced lesions characteristic of the donor HSV-1(MP) strain; recombinants F(MP)C and F(MP)E produced stromal disease approaching the severity of the disease produced by the donor HSV-1(MP) strain, and only recombinants F(MP)A and F(MP)B retained the typically elongate lesions of the recipient HSV-1(F), whereas the recombinant strain F(MP)F produced no disease. The viral functions pertaining to the ocular disease pattern map between 0.70 and 0.83 map units in HSV-1 DNA within the BglII F DNA fragment. The pattern of stromal disease is independent of the production of glycoprotein C and fusion of HEp-2-infected cells. The functions relating to these aspects of ocular disease segregate but are closely linked.
Insights
Genetic factors in herpes simplex virus type 1 (HSV-1) determine ocular disease patterns in rabbits. Recombinant viruses show that specific viral genome regions control ulcer morphology and stromal disease severity, offering insights into HSV-1 pathogenesis.
Area of Science:
- Ophthalmology
- Virology
- Genetics
Background:
- Herpes simplex virus type 1 (HSV-1) causes ocular disease with varying severity.
- The genetic basis for different ocular disease patterns, including epithelial and stromal disease, is not fully understood.
Purpose of the Study:
- To investigate the genetic determinants of ocular disease patterns caused by HSV-1 strains in a rabbit model.
- To map the viral genes responsible for specific disease characteristics like dendritic ulcer morphology and stromal keratitis.
Main Methods:
- Generation of HSV-1 recombinants by transferring defined genomic segments between an epithelial disease-producing strain (HSV-1(F)) and a stromal disease-producing strain (HSV-1(MP)).
- Inoculation of rabbit eyes with wild-type and recombinant HSV-1 strains to assess ocular disease phenotypes.
- Analysis of disease characteristics including ulcer morphology, epithelial disease severity, and stromal disease incidence and duration.
Main Results:
- Recombinant viruses exhibited varying disease patterns, with some inheriting characteristics from the stromal disease-producing parent (HSV-1(MP)).
- Specifically, recombinant F(MP)D mirrored HSV-1(MP) lesions, while F(MP)C and F(MP)E induced significant stromal disease.
- Viral functions controlling ocular disease patterns were mapped to a specific region (0.70-0.83 map units) within the HSV-1 DNA BglII F fragment, independent of glycoprotein C production.
Conclusions:
- The genetic makeup of HSV-1 strains dictates the pattern and severity of ocular disease in rabbits.
- Specific viral genes located within the BglII F fragment are crucial for determining stromal disease and ulcer morphology.
- These findings contribute to understanding HSV-1 pathogenesis and the genetic basis of herpetic eye disease.