Cytopathogenicity, drug susceptibility, and thymidine kinase activity of a retinovirulent herpes simplex virus type 2.
We investigated some of the biological and biochemical characteristics of a neuroinvasive, retinovirulent herpes simplex virus type 2 strain SL (HSV-2[SL]) and compared them with those of a neurovirulent, nonretinovirulent HSV-2 (186). HSV-2(SL) was shown to spread rapidly and produce large syncytium in vitro. HSV-2(SL) and HSV-2(186) were equally susceptible to acyclovir (ACV) and thymine arabinoside (Ara-T). However, HSV-2(SL) was fourfold and 44-fold more susceptible than HSV-2(186) to iododeoxyuridine (IUdR) and bromovinyldeoxyuridine (BVDU), respectively. In addition, cytosolic TK from HSV-2(SL)-infected cells phosphorylated 4, 20, and 23,000 times more IUdR, iododeoxycytidine (IdCyD), and Ara-T than the TK of HSV-2(186), respectively. Further, HSV-2(186) TK did not phosphorylate Ara-T, but HSV-2(186) replication was inhibited by Ara-T. These studies indicate that the retinovirulent HSV-2(SL) has a syn phenotype and a TK with broad substrate activity.
Langford
M P
MP
Department of Ophthalmology, Louisiana State University Medical Center, Shreveport 71130-3932.
Colacino
J M
JM
Kaiwar
R
R
Mahjoub
S B
SB
Ganley
J P
JP
D000212:Acyclovir / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D006801:Humans; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000378:metabolism*
C020235:brivudine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D000212:Acyclovir