Virulence of Herpes Simplex Virus 1 Harboring a UAG Stop Codon between the First and Second Initiation Codon in the Thymidine Kinase Gene

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  • Nguyen Phu Hoang Anh
    Department of Virology 1, National Institute of Infectious Diseases, Japan Department of Developmental Medical Sciences, The University of Tokyo, Japan
  • Yamada Souichi
    Department of Virology 1, National Institute of Infectious Diseases, Japan
  • Harada Shizuko
    Department of Virology 1, National Institute of Infectious Diseases, Japan
  • Fukushi Shuetsu
    Department of Virology 1, National Institute of Infectious Diseases, Japan
  • Mizuguchi Masashi
    Department of Developmental Medical Sciences, The University of Tokyo, Japan
  • Saijo Masayuki
    Department of Virology 1, National Institute of Infectious Diseases, Japan Department of Developmental Medical Sciences, The University of Tokyo, Japan Public Health Office, Health and Welfare Bureau, Sapporo Municipal Government, Japan

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<p>Herpes simplex virus 1 (HSV-1)-TK (8UAG) expresses a truncated thymidine kinase (TK) translated from the second initiation codon due to a stop codon (UAG) at the 8th position (counted from the first initiation codon). Here, we showed that the sensitivity of HSV-1-TK (8UAG) to acyclovir (ACV) is similar to that of the control HSV-1 wild-type (WT), which expresses an intact TK protein. However, HSV-1-TK (44UAG), which expresses a truncated TK due to a UAG codon at position 44, showed lower sensitivity to ACV. A mouse infection model was used to compare the virulence of HSV-1-TK (8UAG) and HSV-1-TK (44UAG) to that of HSV-1 WT. The 50% lethal dose (LD50) for HSV-1-TK (44UAG) was 7.8-fold higher than that for HSV-1-TK (8UAG), whereas the LD50 for HSV-1-TK (8UAG) was the same as that for the parental HSV-1 WT. There were no statistically significant differences among HSV-1-TK (44UAG), HSV-1-TK (8UAG), and HSV-1 WT with respect to replication capacity and viral TK mRNA expression in the mouse brain. Thus, the virulence of HSV-1 expressing the truncated viral TK translated from the second initiation codon might depend on the position of the UAG stop codon.</p>

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