HSV-1 thymidine kinase promotes virulence and latency in the mouse

The relationship between thymidine kinase (TK) activity and virulence was studied in the mouse using three HSV-1 strains: (1) NIH TK+ (100% activity), (2) NIH TK+/- (25% TK activity), and (3) NIH TK- (0% TK activity). Following corneal inoculation, keratitis, virus titers (eye, trigeminal ganglia brain), survival, and latency were determined for each strain. The most virulent strain, NIH TK+ (30% survival) produced the worst keratitis, highest CNS titers, and established latency in 78% of surviving mice. NIH TK+/- demonstrated dose-dependent intermediate virulence (57-90% survival) and established latency in 80% of mice. NIH TK-, the most avirulent strain (93-100% survival) produced eye virus titers equal to the other strains but did not appear to invade the CNS or establish latency. These results indicate that TK gene activity is essential for HSV-1 murine neurovirulence (ie, efficient CNS invasion, replication and establishment of latency), but not for ocular replication.