TY - JOUR
T1 - 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
AU - Inagaki, Takuya
AU - Satoh, Masaaki
AU - Fujii, Hikaru
AU - Yamada, Souichi
AU - Shibamura, Miho
AU - Yoshikawa, Tomoki
AU - Harada, Shizuko
AU - Takeyama, Haruko
AU - Saijo, Masayuki
N1 - Funding Information:
Ethical statement: The animal experiments were conducted in strict accordance with the Guidelines for Proper Conduct of Animal Experiments of the Science Council of Japan and in strict compliance with animal husbandry and welfare regulations under the approval of Animal Care and Use Committee of the National Institute of Infectious Diseases (No. 117026).
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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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U2 - 10.7883/yoken.JJID.2018.176
DO - 10.7883/yoken.JJID.2018.176
M3 - Article
C2 - 29848849
AN - SCOPUS:85056992472
SN - 1344-6304
VL - 71
SP - 343
EP - 349
JO - Japanese Journal of Infectious Diseases
JF - Japanese Journal of Infectious Diseases
IS - 5
ER -
