Two thymidine kinase deficient herpes simplex viruses exhibit unexpected virulence properties

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Updated: Aug 14, 2026

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
11:28

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

Published on: October 7, 2011

K M Izumi1, J G Stevens

  • 1Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024.

Microbial Pathogenesis
|February 1, 1988
PubMed

Insights

Herpes simplex virus type 1 (HSV-1) strains ANG and ANG path showed low thymidine kinase activity but retained neurovirulence. ANG path was neuroinvasive, while ANG was not, suggesting distinct genetic roles in HSV-1 pathogenesis.

Area of Science:

  • Virology
  • Neuroscience
  • Genetics

Background:

  • Herpes simplex virus type 1 (HSV-1) is a significant human pathogen.
  • Thymidine kinase (TK) activity is often associated with HSV-1 neurovirulence.
  • Certain HSV-1 strains exhibit reduced TK activity, necessitating further investigation into their pathogenic potential.

Purpose of the Study:

  • To investigate the neurovirulence and pathogenic characteristics of HSV-1 strains ANG and ANG path, which express low levels of thymidine kinase activity.
  • To compare the neuroinvasive capabilities of ANG and ANG path strains in a murine model.
  • To elucidate the role of specific genes in HSV-1 pathogenesis based on observed virulence differences.

Main Methods:

  • In vitro assessment of thymidine kinase activity and arabinofuranosyl-thymine susceptibility for HSV-1 strains ANG and ANG path.
  • Intracranial inoculation of mice to determine median lethal doses and brain replication profiles.
  • Rear footpad inoculation in mice to evaluate neuroinvasiveness and pathogenesis.

Main Results:

  • HSV-1 strains ANG and ANG path exhibited very low thymidine kinase activity and were resistant to arabinofuranosyl-thymine in vitro.
  • Both ANG and ANG path demonstrated median lethal doses and brain replication patterns similar to the neurovirulent strain 17 syn+ after intracranial inoculation.
  • ANG path exhibited neuroinvasiveness and lethality after peripheral inoculation, whereas ANG did not, indicating differential pathogenic potential.

Conclusions:

  • HSV-1 strains with low thymidine kinase activity can retain significant neurovirulence.
  • ANG path demonstrates neuroinvasiveness, unlike the apparently non-neuroinvasive ANG strain.
  • These findings highlight the complex genetic basis of HSV-1 pathogenesis and neurovirulence.

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