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Journal of Virology, August 2007, p. 8356-8360, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00484-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Expression of Extremely Low Levels of Thymidine Kinase from an Acyclovir-Resistant Herpes Simplex Virus Mutant Supports Reactivation from Latently Infected Mouse Trigeminal Ganglia{triangledown}

Michael I. Besecker,1 Caroline L. Furness,2,{dagger} Donald M. Coen,2 and Anthony Griffiths1,2*

Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227,1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 021152

Received 7 March 2007/ Accepted 10 May 2007

A single-cytosine-deletion in the herpes simplex virus gene encoding thymidine kinase (TK) was previously found in an acyclovir-resistant clinical isolate. A laboratory strain engineered to carry this mutation did not generate sufficient TK activity for detection by plaque autoradiography, which detected 0.25% wild-type activity. However, a drug sensitivity assay suggested that extremely low levels of TK are generated by this virus. The virus was estimated to express 0.09% of wild-type TK activity via a ribosomal frameshift 24 nucleotides upstream of the mutation. Remarkably, this appeared to be sufficient active TK to support a low level of reactivation from latently infected mouse trigeminal ganglia.


* Corresponding author. Mailing address: Dept. of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78227. Phone: (210) 258-9557. Fax: (210) 670-3329. E-mail: agriffiths{at}sfbr.org

{triangledown} Published ahead of print on 23 May 2007.

{dagger} Present address: Grand Union Ward, Department of Paediatrics, St. Mary's Hospital, Praed Street, London W2 1NY, United Kingdom.


Journal of Virology, August 2007, p. 8356-8360, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00484-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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