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Analysis for the pathogenesis of HHV-6 encephalitis in transplant recipients and establishment of guideline for the treatment

Research Project

Project/Area Number 17591120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionFujita Health University

Principal Investigator

YOSHIKAWA Tetsushi  Fujita Health University, School of Medicine, Associate Professor (80288472)

Co-Investigator(Kenkyū-buntansha) ASANO Yoshizo  Fujita Health University, School of Medicine, Professor (40131180)
SUGA Sadao  Fujita Health University, School of Medicine, Associate Professor (70257616)
三宅 史  藤田保健衛生大学, 医学部, 助手 (20367709)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHHV-6 / HSCT / reactivation / encephalitis / cytokine / 造血肝細胞移植
Research Abstract

Although it has been demonstrated that human herpesvirus 6 (HHV-6) reactivation generally occurs approximately 2 to 3 weeks after transplantation in the hematopoietic stem cell transplantation (HSCT) recipients, the mechanism, of viral reactivation remains unclear. To explore the relationship between HHV-6 reactivation and plasma cytokine levels, 24 HSCT recipients underwent measurements of plasma proinflammatory cytokine levels (IL-6, TNF-α, IL-lβ, and IFN-Y), viral isolation, and serological assays. Of these patients, 14 developed an HHV-6 reactivation, and 9 developed HHV-6 viremia approximately 2 to 3 weeks after transplantation. IL-6 levels were significantly higher in the recipients with an HHV-6 reactivation than in the subjects without an HHV-6 reactivation at 1 week, 2 Weeks, and 4 weeks after transplantation. In addition, the level of TNF-α was significantly higher in recipients with an HHV-6 reactivation than in those without an HHV-6 reactivation at 2 weeks post-transplantation. Low levels of IL-1β and IFN-Y were detected in small number of the plasma samples, although there were no significant differences between the two groups in the levels of these cytokines. These results imply that proinflammatory cytokines, in particular IL-6 and TNF-α, play a role in the pathogenesis of HHV-6 reactivation after HSCT.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (47 results)

All 2008 2007 2006 2005 Other

All Journal Article (31 results) (of which Peer Reviewed: 11 results) Presentation (16 results)

  • [Journal Article] Human herpesvirus 6 infection in adult living related liver transplant recipients2008

    • Author(s)
      Ohashi M., et. al.
    • Journal Title

      Liver Transplant 14

      Pages: 100-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human herpesvirus 6 infection in adult living related liver transplant recipients.2008

    • Author(s)
      Ohashi M., et. al.
    • Journal Title

      Liver Transplant 14

      Pages: 100-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human herpesvirus 6 infection in adult living related liver transplant recipients.2008

    • Author(s)
      Ohashi M, et. al.
    • Journal Title

      Liver Transplant 14

      Pages: 100-9

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method2007

    • Author(s)
      Ihira M., et. al.
    • Journal Title

      J Clin Virol 39

      Pages: 22-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method.2007

    • Author(s)
      Mira M., et. al.
    • Journal Title

      J Clin Virol 39

      Pages: 22-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method.2007

    • Author(s)
      Ihira M, et. al.
    • Journal Title

      J Clin Virol 39

      Pages: 22-6

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 DNA in samples from transplant recipients by multiplex real-time PCR assay.2007

    • Author(s)
      Wada K, et. al.
    • Journal Title

      J Clin Microbiol 45

      Pages: 1426-32

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Latent infection of human herpesvirus 7 in CD4+ T lymphocytes2006

    • Author(s)
      Miyake F., et. al.
    • Journal Title

      J Med Virol 78

      Pages: 112-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] HHV 6 reactivation in trichloroethylene-exposed workers suffering from generalized skin disorders accompanying hepatic dysfunction2006

    • Author(s)
      Huang H., et. al.
    • Journal Title

      J Occup Health 48

      Pages: 417-23

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Time course characteristics of HHV-6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum2006

    • Author(s)
      Kumagai T., et. al.
    • Journal Title

      J Med Virol 78

      Pages: 792-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human herpesvirus 6 reactivation and inflammatory cytokines in patients with drug induced hypersensitivity syndrome2006

    • Author(s)
      Yoshikawa T., et. al.
    • Journal Title

      J Clin Virol 37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Latent infection of human herpesvirus 7 in CD4+T lymphocytes.2006

    • Author(s)
      Miyake F., et. al.
    • Journal Title

      J Med Virol 78

      Pages: 112-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] HHV 6 reactivation in trichloroethylene-exposed workers suffering from generalized skin disorders accompanying hepatic dysfunction.2006

    • Author(s)
      Huang H., et. al.
    • Journal Title

      J Occup Health 48

      Pages: 417-423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Time course characteristics of HHV-6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum.2006

    • Author(s)
      Kumagai T., et. al.
    • Journal Title

      J Med Virol 78

      Pages: 792-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human herpesvirus 6 reactivation and inflammatory cytokines in patients with drug induced hypersensitivity syndrome.2006

    • Author(s)
      Yoshikawa T., et. al.
    • Journal Title

      J Clin Virol 37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Latent infection of human herpesvirus 7 in CD4+ T lymphocytes.2006

    • Author(s)
      Miyake F, et al.
    • Journal Title

      J Med Virol 78

      Pages: 112-116

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Human herpesvirus 6 reactivation in trichloroethylene-exposed workers suffering. from generalized skin disorders accompanying hepatic dysfunction.2006

    • Author(s)
      Huang H, et al.
    • Journal Title

      J Occup Health 48

      Pages: 417-423

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Drug-Induced Hypersensitivity Syndrome due to Mexiletine Hydrochloride Associated with Reactivation of Human Herpesvirus 7.2006

    • Author(s)
      Yagami A. et al.
    • Journal Title

      Dermatology. 213

      Pages: 341-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Human herpesvirus 6 reactivation and inflammatory cytokines in patients with drug induced hypersensitivity syndrome.2006

    • Author(s)
      Yoshikawa T, et al.
    • Journal Title

      J Clin Virol 37

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Latent infection of human herpesvirus 7 in CD4+ T lymphocytes.2006

    • Author(s)
      Miyake F, Yoshikawa T, Sun H, et al.
    • Journal Title

      Journal of Medical Virology 78

      Pages: 112-116

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of shedding of 3 β herpesviruses in saliva from patients with connective tissue diseases2005

    • Author(s)
      Yoshikawa T., et. al.
    • Journal Title

      J Infect Dis 192

      Pages: 1530-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Postinfectious myeloradiculoneuropathy with cranial nerve involvements associated with human herpesvirus 7 infection2005

    • Author(s)
      Mihara T., et. al.
    • Journal Title

      Arch Neurol 62

      Pages: 1755-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Analysis of shedding of 3 β herpesviruses in saliva from patients with connective tissue diseases.2005

    • Author(s)
      Yoshikawa T., et. al.
    • Journal Title

      J Infect Dis 192

      Pages: 1530-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Postinfectious myeloradiculoneuropathy with cranial nerve involvements associated with human herpesvirus 7 infection.2005

    • Author(s)
      Mihara T., et. al.
    • Journal Title

      Arch Neuro1. 62

      Pages: 1755-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Analysis of shedding of 3 β herpesviruses in saliva from patients with connective tissue diseases.2005

    • Author(s)
      Yoshikawa T, Ihira M, Taguchi H, et al.
    • Journal Title

      Journal of Infectious Diseases 192

      Pages: 1530-1536

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rapid diagnosis of herpes simplex virus infection by loop-mediated isothermal amplification method.2005

    • Author(s)
      Enomoto Y, Yoshikawa T, Ihira M, et al.
    • Journal Title

      Journal of Clinical Microbiology 43

      Pages: 951-955

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In-vitro and in-vivo analysis for expression of human herpesvirus 6 U90 protein.2005

    • Author(s)
      Nishimura N, Yoshikawa T, Ozaki T, et al.
    • Journal Title

      Journal of Medical Virology 75

      Pages: 86-92

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Comparison of loop-mediated isothermal amplification, real-time PCR and virus isolation for detection of herpes simplex virus in genital lesions.2005

    • Author(s)
      Sugiyama H, Yoshikawa T, Ihira M, et al.
    • Journal Title

      Journal of Medical Virology 75

      Pages: 583-587

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rapid detection of herpes simplex virus DNA in cerebrospinal fluid : comparison between loop-mediated isothermal amplification and real-time PCR.2005

    • Author(s)
      Kimura H, Ihira M, Enomoto Y, et al.
    • Journal Title

      Medical Microbiology Immunology 194

      Pages: 181-185

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method.

    • Author(s)
      Ihira M, et al.
    • Journal Title

      J Clin Virol (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rapid detection of human herpesvirus 8 DNA using loop-mediated isothermal amplification.

    • Author(s)
      Kuhara T, et al.
    • Journal Title

      J Virol Method (In press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] National survey of exanthem subitum associated encephalitis in Japan.2007

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      45th Annual Meeting of IDSA
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2007-10-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] ヒトヘルペスウイルス6(HHV-6)関連脳炎脳症の全国調査2007

    • Author(s)
      吉川 哲史, 他
    • Organizer
      第110回日本小児科学会学術集会
    • Place of Presentation
      京都、京都府
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Reactivation of three essential herpesviruses(CMV,HHV-6,and EBV) in hematopoietic stem cell transplant recipients2007

    • Author(s)
      Ihira M., et. al.
    • Organizer
      IDSA 45th Annual Meeting
    • Place of Presentation
      San Diego,California
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] National survey of exanthema subitum associated encephalitis/encephalopathy in Japan2007

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      IDSA 45th Annual Meeting
    • Place of Presentation
      San Diego,California
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] HHV-6脳炎、脳症の発症メカニズム解析2007

    • Author(s)
      吉川 哲史, 他
    • Organizer
      第39回日本小児感染症学会
    • Place of Presentation
      横浜、神奈川県
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Reactivation of three essential herpesviruses(CMV, HHV-6, and EBV) in hematopoietic stem cell transplant recipients.2007

    • Author(s)
      Ibira M., et. al.
    • Organizer
      45th Annual Meeting of the IDSA
    • Place of Presentation
      San Diego, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism for reactivation of human herpesvirus 6 in transplant recipients2006

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      5th International Conference on HHV-6 and 7
    • Place of Presentation
      Barcelona,Spain
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Human herpesvirus 6 infection in adult living related liver transplant recipients2006

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      International Herpesvirus Workshop
    • Place of Presentation
      Seattle,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Direct detection of human herpesvirus 6 DNA in serum by loop-mediated isothermal amplification2006

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      44th Annual Meeting of the IDSA
    • Place of Presentation
      Toronto,Canada
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒトヘルペスウイルス6(HHV6)関連脳炎脳症の全国調査(第二報)2006

    • Author(s)
      大橋 正博, 他
    • Organizer
      第38回日本小児感染症学会
    • Place of Presentation
      高知、高知県
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヘルペスウイルスとヒトの病気:HHV-6の発見が臨床医に与えたインパクト2006

    • Author(s)
      吉川 哲史
    • Organizer
      第54回日本ウイルス学会
    • Place of Presentation
      名古屋、愛知県
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism for reactivation of human herpesvirus 6 in transplant recipients.2006

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      5th International Conference on HHV-6 and 7
    • Place of Presentation
      Barcelona, Spain
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Human herpesvirus 6 infection in adult living related liver transplant recipients.2006

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      International Herpesvirus Workshop
    • Place of Presentation
      Seattle, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Direct detection of human herpesvirus 6 DNA in serum by loop-mediated isothermal amplification.2006

    • Author(s)
      Yoshikawa T., et. al.
    • Organizer
      44th Annual Meeting of the IDSA
    • Place of Presentation
      Toronto, Canada
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒトヘルペスウイルス6脳炎の全国調査2005

    • Author(s)
      大橋 正博, 他
    • Organizer
      第37回日本小児感染症学会
    • Place of Presentation
      津、三重県
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 同種造血幹細胞移植患者におけるHHV-6感染の発症メカニズム解析:炎症性サイトカインとの関連性2005

    • Author(s)
      藤田 彩乃, 他
    • Organizer
      第53回日本ウイルス学会
    • Place of Presentation
      横浜、神奈川県
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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