ANALYSIS OF THE RELATIONSHIP BETWEEN CELLULAR THYMIDINE KINASE-ACTIVITY AND VIRULENCE OF THYMIDINE KINASE-NEGATIVE HERPES-SIMPLEX VIRUS TYPE-1 AND TYPE-2

The virulence of thymidine kinase-negative herpes simplex virus type 1 (HSV-1; VRTK(-) strain) and type 2 (HSV-2; UWTK- strain) was studied in comparison with that of their parental strains (VR-3 and UW-268, respectively) in an encephalitis model of adult (4-week-old) and newborn (3-day-old) mice. Viral thymidine kinase (TK) activity was essential for the maximum expression of virulence of HSV-1, because the 50% lethal dose (LD(50)) of VRTK(-) was 60 times higher than that of VR-3 in the brains of newborn mice expressing high levels of cellular TK activity. However, the UWTK- strain showed the same virulence as the parental strain in newborn mice, despite the lack virulence in adults, suggesting that replication of the UWTK- strain was completely supported by cellular TK activity. This difference in the role of viral and-cellular TKs for virus growth between HSV-1 and HSV-2 was confirmed with the one-step growth of virus strains in L-M and L-M(TK-) cells.