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Restoration of wild-type pathogenicity to an attenuated DNA polymerase mutant of herpes simplex virus type 1
Abstract:
The drug-resistant variant, RSC-26, which was derived from the herpes simplex virus type 1 wild-type strain SC16, expresses an altered DNA polymerase and has reduced pathogenicity in animal models. To determine whether the attenuation in pathogenicity was due solely to mutation in the polymerase gene, a fragment of the wild-type gene was cloned, transferred into the genome of RSC-26 and recombinants were isolated. Three recombinants examined had similar properties to wild-type virus with respect to their sensitivity to antiviral drugs, DNA polymerase activities and their pathogenicity for mice. These results strongly suggest that expression of the altered polymerase of RSC-26 results in attenuated pathogenicity.
Insights
The altered DNA polymerase in herpes simplex virus type 1 (HSV-1) variant RSC-26 reduces its pathogenicity. Reintroducing the wild-type polymerase gene restored pathogenicity, confirming the polymerase
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Herpes simplex virus type 1 (HSV-1) variant RSC-26 exhibits drug resistance and reduced pathogenicity.
- This variant expresses an altered DNA polymerase enzyme.
- Previous studies suggest a link between polymerase mutation and reduced pathogenicity.
Purpose of the Study:
- To ascertain if the attenuated pathogenicity of HSV-1 RSC-26 is solely due to its altered DNA polymerase.
- To investigate the role of the DNA polymerase gene in HSV-1 pathogenicity.
Main Methods:
- Cloning of a wild-type DNA polymerase gene fragment from HSV-1 SC16.
- Transfer of the wild-type gene fragment into the genome of HSV-1 RSC-26.
- Isolation and characterization of resulting recombinant viruses.
Main Results:
- Three isolated recombinants exhibited properties similar to the wild-type HSV-1 SC16.
- Recombinants showed restored sensitivity to antiviral drugs.
- Recombinants demonstrated restored DNA polymerase activity and pathogenicity in mice.
Conclusions:
- The altered DNA polymerase in HSV-1 RSC-26 is directly responsible for its attenuated pathogenicity.
- Restoration of the wild-type polymerase gene reverses the reduction in pathogenicity.
- This highlights the critical role of the DNA polymerase in HSV-1 virulence.