%0 Journal Article %A Harris, Wendy %A Collins, Peter %A Fenton, Rob J. %A Snowden, Wendy %A Sowa, Mike %A Darby, Graham %T Phenotypic and genotypic characterization of clinical isolates of herpes simplex virus resistant to aciclovir %D 2003 %J Journal of General Virology, %V 84 %N 6 %P 1393-1401 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.18880-0 %I Microbiology Society, %X A panel of 10 clinical isolates of herpes simplex virus (HSV) deficient in the expression of thymidine kinase (TK) and phenotypically resistant to aciclovir was characterized. Sequence analysis revealed a variety of mutations in TK (nucleotide substitutions, insertions and deletions), most of which resulted in truncated TK polypeptides. In line with previous reports, the most common mutation was a single G insertion in the ‘G-string’ motif. One HSV-1 isolate and two HSV-2 isolates appeared to encode full-length polypeptides and, in each case, an amino acid substitution likely to be responsible for the phenotype was identified. Pathogenicity was determined using a zosteriform model of HSV infection in BALB/c mice. The majority of isolates appeared to show impaired growth at the inoculation site compared with wild-type virus. They also showed poor replication in the peripheral nervous system and little evidence of zosteriform spread. One exception was isolate 4, which had a double G insertion in the G-string but, nevertheless, exhibited zosteriform spread. These studies confirmed that TK-deficient viruses display a range of neurovirulence with respect to latency and zosteriform spread. These results are discussed in the light of previous experience with TK-deficient viruses. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.18880-0