title: Expression of extremely low levels of thymidine kinase from an acyclovir-resistant herpes simplex virus mutant supports reactivation from latently infected mouse trigeminal ganglia.
abstract: 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.
authors.affiliation: Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Besecker
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Furness
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
authors.forename: Anthony
authors.initials: A
authors.lastname: Griffiths
mesh_terms: D000212:Acyclovir / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D001483:Base Sequence; D024882:Drug Resistance, Viral; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000821:virology*; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir