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Updated: Aug 11, 2026
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice
Abstract:
The pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site of inoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain.
Insights
Herpes simplex virus mutants lacking thymidine kinase are less virulent in mice. These mutants can establish latent infections and confer immunity against parent strains.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Herpes simplex virus (HSV) is a significant human pathogen.
- Thymidine kinase (TK) is a viral enzyme crucial for HSV replication and pathogenicity.
- Understanding the role of TK in HSV pathogenesis is vital for developing antiviral strategies.
Purpose of the Study:
- To compare the pathogenicity of HSV-1 and HSV-2 mutants lacking thymidine kinase (TK) with their parent strains in a mouse model.
- To investigate viral replication and neuroinvasion following different inoculation routes.
- To assess the potential of TK-deficient mutants in inducing protective immunity.
Main Methods:
- Intracerebral and peripheral inoculation of mice with HSV-1 and HSV-2 TK-deficient mutants and their parent strains.
- Monitoring of viral pathogenicity and replication at inoculation sites and in the nervous system.
- Evaluation of immune response and protection against subsequent challenge with virulent parent strains.
Main Results:
- HSV-1 and HSV-2 TK-deficient mutants exhibited significantly reduced virulence compared to parent strains after both intracerebral and peripheral inoculation.
- Viral replication was diminished at the inoculation site for the mutant strains.
- A high-dose inoculation of the HSV-1 mutant in the ear led to latent infection in cervical dorsal root ganglia.
- Mice inoculated intracerebrally with low doses of mutant viruses developed solid immunity against lethal doses of the parent strains.
Conclusions:
- Thymidine kinase is essential for the full pathogenicity of HSV-1 and HSV-2 in mice.
- TK-deficient HSV mutants are significantly attenuated and can establish latent infections.
- Intracerebral inoculation with low doses of TK-deficient HSV mutants can induce robust protective immunity against virulent HSV infection, suggesting their potential as vaccine candidates.
