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The Role of Herpes Simplex Virus Thymidine Kinase Expression in Pathogenesis and Latency

  • Richard B. Tenser
Part of the Frontiers of Virology book series (FRVIROLOGY, volume 3)

Summary

The role of herpes simplex virus (HSV) thymidine kinase (TK) expression for HSV neurovirulence and latency has been evaluated by many investigators. Although neurovirulence is complex and involves multiple host and viral factors, in studies with HSV TK-negative (TK) mutants, it seemed that TK expression was an important factor. This was apparent in experimental animal studies, as indicated by decreased replication of TK HSV mutants in neural tissue and by decreased mortality. Although some virulent TK HSV mutants have been reported, most investigators, including studies with HSV deletion mutants, have supported an important role for HSV TK expression and neurovirulence.

In early experimental animal studies in which HSV latency was defined by the ability to recover HSV from explants of latently infected ganglia, HSV TK expression also seemed important for latency. In more recent studies in which molecularly constructed TK HSV mutants were utilized, it was evident that ganglia could be infected with TK HSV so that HSV latency-associated transcript (LAT) was detected in ganglia during the period of latency. As in most previous studies, reactivation of TK HSV was not usually detected in ganglion explants. TK HSV could be rescued from such ganglia, however, by superinfection-complementation with TK+ HSV. These observations suggested that HSV TK expression was important for the reactivation of HSV from latent sensory ganglion neuron infection.

In recent, more speculative studies, the HSV tk gene and HSV TK mutants have been utilized therapeutically in experimental animal studies. In some of these studies, HSV TK expression was induced in neoplastic cells, which were then destroyed by TK-mediated antivirals. In other studies, TK HSV was used to destroy rapidly growing tumor cells or, alternatively, TK HSV was used to incorporate foreign genes into the nervous system.

Keywords

Herpes Simplex Virus Type Thymidine Kinase Trigeminal Ganglion Thymidine Kinase Gene Thymidine Kinase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Richard B. Tenser
    • 1
  1. 1.Department of Medicine (Neurology) and Microbiology and ImmunologyPennsylvania State University College of MedicineHersheyUSA

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