New Mechanism of Acyclovir Resistance of Herpes Simplex Virus 1, Which Has an Amber UAG Codon Between the First and Second AUG Initiation Codons.

New Mechanism of Acyclovir Resistance of Herpes Simplex Virus 1, Which Has an Amber UAG Codon Between the First and Second AUG Initiation Codons. Jpn J Infect Dis. 2020 Jun 30;: Authors: Nguyen PHA, Yamada S, Shibamura M, Inagaki T, Fujii H, Harada S, Fukushi S, Mizuguchi M, Saijo M Abstract 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 differe...
Source: Japanese Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: Jpn J Infect Dis Source Type: research