Herpes simplex virus thymidine kinase expression in trigeminal ganglion infection: Correlation of enzyme activity with ganglion virus titer and evidence of in vivo complementation

Richard B. Tenser, Steven Ressel, Marie E. Dunstan

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45 Scopus citations

Abstract

Experimental trigeminal ganglion and corneal infection in mice was studied with three thymidine kinase-positive (TK+) strains of herpes simplex virus type 1 (HSV-1) and eight TK- HSV-1 mutants. Viruses were extensively tested in cell culture to determine whether any were temperature sensitive (ts) for virus replication or for TK activity. TK- mutants were no more ts than were TK+ viruses. By arabinosylthymine testing and measurement of thymidine phosphorylation, it was apparent that some TK- mutants were, in fact, intermediate for TK activity (TK±). After corneal inoculation of individual viruses it was observed with one exception that TK-, TK±, and TK+ viruses replicated in ocular tissues (3 days postinoculation, 2.2 × 103-1.1 × 105 PFU/eye). However, TK- mutants were rarely isolated from trigeminal ganglia (<2.5-<5.6 × 10-1 PFU/mg), whereas TK+ and to a lesser degree TK± viruses were frequently (1.2 × 103-1.2 × 104 PFU/mg and 3.2 × 100-2.1 × 103 PFU/mg). In vivo complementation studies were performed by corneal inoculation of TK--TK- and TK--TK- virus mixtures. TK+ HSV complemented TK- virus since significant amounts of TK- HSV were isolated from trigeminal ganglia (complementation indices were >60->1600). In addition, after inoculation of certain TK--TK- pairs, complementation in ganglia was observed (complementation indices were >2.4->120). These studies support the hypothesis that HSV-1 TK expression is necessary for sensory ganglion (neuron) infection in three ways: HSV-1 TK mutants that replicated in ocular tissues and were not ts mutants did not replicate in vivo in trigeminal ganglia; (ii) there was a correlation between level of viral TK activity and trigeminal ganglion virus titer; and (iii) when complemented by TK+ or TK- HSV, TK- virus replicated in trigeminal ganglia.

Original languageEnglish (US)
Pages (from-to)328-341
Number of pages14
JournalVirology
Volume112
Issue number1
DOIs
StatePublished - Jul 15 1981

All Science Journal Classification (ASJC) codes

  • Virology

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