@article{APS8292,
author = {Nan HU and Hiroshi SHIOTA},
title = {Emergence of resistance to carbocyclic oxetanocin G in herpes simplex virus type 1 and genetic analysis of resistant mutants},
journal = {Acta Pharmacologica Sinica},
volume = {25},
number = {7},
year = {2016},
keywords = {},
abstract = {AIM:
To elucidate the potentiality of emergence of drug-resistance to carbocyclic oxetanocin G (C.OXT-G), a new effective antiviral drug for herpetic keratitis during treatment and the mechanism of this drug resistance.
METHODS:
A C.OXT-G resistant strain (C.OXT-Gr) was established by serially propagating the herpes simplex virus (HSV) -1 in African green monkey kidney (VERO) cells in the presence of C.OXT-G. After the drug sensitivity assay and the thymidine kinase (TK) activity assay, the molecular basis for the drug resistance was studied using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and PCR direct sequencing technology.
RESULTS:
After the 10th passage in 10 microm C.OXT-G, the ED50 of the C.OXT-Gr was 17.08-fold greater than that of the original strain on the average and the TK activities of these resistant strains were extremely reduced. PCR-SSCP analysis on TK gene of the wild HSV-1 and the C.OXT-Gr showed altered migration patterns in part 3 and part 4, while PCR-SSCP analysis on DNA polymerase gene showed no difference among the viruses. Sequence analysis revealed a deletion of G at position of 430 that caused frameshift, resulting in premature termination in the TK gene.
CONCLUSION:
The drug resistance to C.OXT-G may appear during the treatment due to the deficiency of TK activity caused by a single mutation in the TK gene of HSV-1.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/8292}
}