Acyclovir sensitivity and neurovirulence of herpes simplex virus type 1 with amino acid substitutions in the viral thymidine kinase gene, which were detected in the patients with intractable herpes simplex encephalitis previously reported

Takuya Inagaki, Masaaki Satoh, Hikaru Fujii, Souichi Yamada, Miho Shibamura, Tomoki Yoshikawa, Shizuko Harada, Haruko Takeyama, Masayuki Saijo

    Research output: Contribution to journalArticle

    Abstract

    Several cases of herpes simplex encephalitis (HSE) caused by acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) have been reported. Amino acid substitutions of R41H, Q125H, and A156V in the viral thymidine kinase (vTK) gene have been reported to confer ACV resistance. Recombinant HSV-1 clones, containing each amino acid substitution in the vTK gene, were generated using the bacterial artificial chromosome system. A recombinant HSV-1 with the Q125H substitution showed ACV resistance while the R41H or A156V substitutions were ACV-sensitive. Furthermore, the Q125H recombinant HSV-1 was less virulent than the repaired virus, but it maintained neurovirulence in mice at relatively high levels. Substitution of Q125H, which was detected in the neonatal HSE patient, conferred ACV resistance, but the substitutions of R41H and A156V, which were detected in immunocompetent adult HSE patients, did not. This suggests that HSE caused by ACV-resistant HSV-1 might be a very rare event to occur during the course of ACV treatment in immunocompetent patients. Showing resistance to ACV treatment does not always indicate emergence of ACV-resistant HSV-1 in HSE patients.

    Original languageEnglish
    Pages (from-to)343-349
    Number of pages7
    JournalJapanese Journal of Infectious Diseases
    Volume71
    Issue number5
    DOIs
    Publication statusPublished - 2018 Jan 1

    Fingerprint

    Herpes Simplex Encephalitis
    Acyclovir
    Thymidine Kinase
    Human Herpesvirus 1
    Amino Acid Substitution
    Genes
    Bacterial Artificial Chromosomes
    Clone Cells
    Viruses

    ASJC Scopus subject areas

    • Microbiology (medical)
    • Infectious Diseases

    Cite this

    Acyclovir sensitivity and neurovirulence of herpes simplex virus type 1 with amino acid substitutions in the viral thymidine kinase gene, which were detected in the patients with intractable herpes simplex encephalitis previously reported. / Inagaki, Takuya; Satoh, Masaaki; Fujii, Hikaru; Yamada, Souichi; Shibamura, Miho; Yoshikawa, Tomoki; Harada, Shizuko; Takeyama, Haruko; Saijo, Masayuki.

    In: Japanese Journal of Infectious Diseases, Vol. 71, No. 5, 01.01.2018, p. 343-349.

    Research output: Contribution to journalArticle

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    abstract = "Several cases of herpes simplex encephalitis (HSE) caused by acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) have been reported. Amino acid substitutions of R41H, Q125H, and A156V in the viral thymidine kinase (vTK) gene have been reported to confer ACV resistance. Recombinant HSV-1 clones, containing each amino acid substitution in the vTK gene, were generated using the bacterial artificial chromosome system. A recombinant HSV-1 with the Q125H substitution showed ACV resistance while the R41H or A156V substitutions were ACV-sensitive. Furthermore, the Q125H recombinant HSV-1 was less virulent than the repaired virus, but it maintained neurovirulence in mice at relatively high levels. Substitution of Q125H, which was detected in the neonatal HSE patient, conferred ACV resistance, but the substitutions of R41H and A156V, which were detected in immunocompetent adult HSE patients, did not. This suggests that HSE caused by ACV-resistant HSV-1 might be a very rare event to occur during the course of ACV treatment in immunocompetent patients. Showing resistance to ACV treatment does not always indicate emergence of ACV-resistant HSV-1 in HSE patients.",
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