DOI: 10.1073/pnas.77.4.2270. Resistance of herpes simplex virus to acycloguanosine: role of viral thymidine kinase and DNA polymerase loci.

Resistance of herpes simplex virus to acycloguanosine: role of viral thymidine kinase and DNA polymerase loci.

10.1073/pnas.77.4.2270

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Acycloguanosine [9-(2-hydroxyethoxymethyl)guanine; acyclo-Guo] is a potent inhibitor of herpes simplex viruses (HSV); it is selectively phosphorylated in virus-infected cells. In order to define those viral functions that may mediate resistance to acyclo-Guo, the drug sensitivities of temperature-sensitive (ts) and phosphonoacetic acetic acid (PAA)-resistant mutants of HSV-1 and HSV-2 have been determined. Two distinct viral genetic loci are independently associated with acyclo-Guo resistance. Mutations resulting in diminished thymidine kinase activity are associated with resistance to inhibition by acyclo-Guo. Several PAA-resistant viruses that express wild-type levels of thymidine kinase activity are also resistant to acyclo-Guo. This suggests the importance of the viral DNA polymerase region in mediating acyclo-Guo resistance and is consistent with a close relationship between the PAAr mutation site and the AGGr locus. When wild-type HSV-1 is serially propagated under the selective pressure of acyclo-Guo, rapid emergence of resistant virus occurs, accompanied by the simultaneous appearance of thymidine kinase-deficient progeny.

Authors 2

L E Schnipper (first)
C S Crumpacker (additional)

References 0 Referenced 138

None

Dates

Type	When
Created	19 years, 2 months ago (May 31, 2006, 4:13 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 11:21 a.m.)
Indexed	4 months, 3 weeks ago (April 4, 2025, 6:42 p.m.)
Issued	45 years, 4 months ago (April 1, 1980)
Published	45 years, 4 months ago (April 1, 1980)
Published Online	45 years, 4 months ago (April 1, 1980)
Published Print	45 years, 4 months ago (April 1, 1980)

Funders 0

None

BibTeX

@article{Schnipper_1980, title={Resistance of herpes simplex virus to acycloguanosine: role of viral thymidine kinase and DNA polymerase loci.}, volume={77}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.77.4.2270}, DOI={10.1073/pnas.77.4.2270}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Schnipper, L E and Crumpacker, C S}, year={1980}, month=apr, pages={2270–2273} }

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