HSV-1 latency: thymidine kinase requirement and the round-trip theory.
The present study used the rabbit iontophoresis model to examine the thymidine kinase (TK) requirement for HSV-1 latency, and test the round trip theory of latency with emergent phenotypic mutations of the HSV-1 TK negative (TK-) inoculating strain. The results demonstrated repeated induced ocular shedding of latent HSV-1 in 14-100% of rabbits. The TK phenotype of recovered tear film following spontaneous shedding and repeated iontophoresis induction was thymidine kinase negative in 90% of eyes. Sequential shedding of TK- virus from the same eye over time was demonstrated in 21% of eyes in 33% of rabbits. We conclude that TK is not an absolute requirement for the establishment or reactivation of latent HSV-1 in the rabbit model. The round trip theory of latency was not supported as TK+ isolates and syncytial variants of the TK- inoculating strain which were recovered at the ocular surface after the initial iontophoresis could not be demonstrated following subsequent trials of iontophoresis.
D000818:Animals; D005123:Eye / Q000382:microbiology; D005260:Female; D007478:Iontophoresis; D010641:Phenotype; D011817:Rabbits; D018139:Simplexvirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D013937:Thymidine Kinase / Q000494:pharmacology*; D013997:Time Factors; D014775:Virus Activation / Q000187:drug effects*
D013937:Thymidine Kinase