Pathogenicity of herpes simplex virus mutants containing drug resistance mutations in the viral DNA polymerase gene

Area of Science:

• Virology
• Genetics
• Neuroscience

Background:

• Herpes simplex virus (HSV) is a common human pathogen.
• HSV DNA polymerase is a target for antiviral drugs.
• Understanding viral replication and pathogenicity is crucial for developing treatments.

Purpose of the Study:

• To evaluate the replication and pathogenicity of HSV mutants with drug resistance mutations.
• To assess the impact of these mutations on viral behavior in different host tissues.
• To investigate potential sequelae of infection with these mutants.

Main Methods:

• Generation of three HSV mutants with drug resistance mutations in the DNA polymerase gene.
• Inoculation of mice in the ear and intracerebrally with wild-type and mutant HSV.
• Assessment of viral replication in the ear.
• Evaluation of pathogenicity and survival rates after intracerebral inoculation.
• Observation of clinical signs, including cataract development.

Main Results:

• HSV mutants replicated without significant reduction in the ears of mice compared to wild-type.
• Intracerebral inoculation with mutants resulted in attenuated pathogenicity.
• Cataracts were a common complication in mice that survived mutant infections.

Conclusions:

• Drug resistance mutations in HSV DNA polymerase do not impair viral replication in peripheral sites like the ear.
• These mutations can attenuate HSV pathogenicity in the central nervous system.
• Cataract formation is a potential sequela of HSV infection with these mutants, suggesting neurological involvement.