Article ID: JJID.2020.313
The morphological changes in structure of HSV-1 viral thymidine kinase (vTK) polypeptide usually leads to conferring acyclovir (ACV)-resistance. HSV-1 I4-2, in which an amber UAG stop codon is present at the 8th position between the 1st initiation AUG codon (1st position) and the 2nd initiation AUG codon (46th position) of HSV-1 vTK gene, showed sensitivity to acyclovir (ACV), whereas HSV-1 KG111, in which an amber codon was artificially inserted at the 44th position, showed resistance to ACV at 39˚C. The mechanism for the difference in the sensitivity profiles was elucidated. The virus recombinants HSV-1-TK(8UAG) and HSV-1-TK(44UAG) containing an amber codon at the 8th and 44th positions counted from the 1st initiation codon, respectively, were generated and tested for susceptibility to antiviral compounds. HSV-1-TK(8UAG) and HSV-1-TK(44UAG) were sensitive and resistant to ACV and BVdU at 37˚C, respectively. The expression level of the truncated viral thymidine kinase translated from the 2nd initiation codon in Vero cells infected with HSV-1-TK(44UAG) was clearly less than that with HSV-1-TK(8UAG) in a temperature-dependent manner. The differences in the antiviral sensitivity profiles were due to the position of the amber UAG codon between the 1st and the 2nd initiation codons.
