Analysis of the relationship between cellular thymidine kinase activity and virulence of thymidine kinase-negative herpes simplex virus types 1 and 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 (LD50) 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 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.
Suzutani
T
T
Department of Microbiology, Asahikawa Medical College, Hokkaido, Japan.
Koyano
S
S
Takada
M
M
Yoshida
I
I
Azuma
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002478:Cells, Cultured; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity*; D018258:Herpesvirus 2, Human / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D014774:Virulence
D013940:Thymidylate Synthase; D013937:Thymidine Kinase