Research on the pathophysiology and treatment for neonate with drug-resistant herpes simplex virus infections

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09675
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SAIJO MASAYUKI 国立感染症研究所, ウイルス第一部, 部長 (50300926)
• Research Collaborator: Fujii Hikaru 国立感染症研究所, ウイルス第一部, 流動研究員 ; Yamada Souichi 国立感染症研究所, ウイルス第一部, 主任研究官 ; Harada Shizuko 国立感染症研究所, ウイルス第一部, 主任研究官 ; Omura Natsumi 国立感染症研究所, ウイルス第一部, 実習生 ; Yoshikawa Tomoki 国立感染症研究所, ウイルス第一部, 主任研究官
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 単純ヘルペスウイルス1型 / 新生児ヘルペス / ヘルペス脳炎 / アシクロビル / 薬剤耐性 / 神経病原性 / チミジンリン酸化酵素

Outline of Final Research Achievements

In our previous study, the amino acid substitution of H from Q at the 125th position of viral thymidine kinase (vTK) gene amplified from the central spinal fluid (CSF) of neonatal HSV-1 infection was confirmed to confer acyclovir (ACV)-resistance. In this study, recombinant HSV-1 with the mutation in vTK gene was generated artificially by using BAC system. The recombinant HSV-1 showed ACV-resistance in vitro, but maintained neurovirulence in mouse infection model. The sensitivity of ACV-resistant HSV-1 to ACV was confirmed to be associated significantly with the neurovirulence in mouse infection model, being that the higher the resistance, lower the neurovirulence in mice. The present study indicates that virological test of and selection of proper treatment for the patients, who showed intractable HSV-1 disease against ACV-therapy, are required,

Free Research Field

ウイルス学，小児科学，感染症学