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
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 were reported to confer ACV-resistance. Recombinant HSV-1 clones with each amino acid substitution in the vTK were generated using the bacterial artificial chromosome (BAC) system. A recombinant HSV-1 with the substitution of Q125H showed ACV-resistance, while those of R41H or A156V were sensitive to ACV. Furthermore, a recombinant HSV-1 with the substitution of Q125H was less virulent than the repaired virus, but maintained neurovirulence in mice at relatively high level. 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 the immunocompetent adult HSE patients, did not. This suggests that HSE caused by ACV-resistant HSV-1 during the course of ACV-treatment might be a very rare event in immunocompetent patients. Showing resistance to ACV-treatment does not always indicates emergence of ACV-resistant HSV-1 in HSE patients.
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