• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of attenuated herpes simplex virus vector for analysis of neurological functions.

Research Project

Project/Area Number 13558094
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Neurochemistry/Neuropharmacology
Research InstitutionToyama Medical and Pharmaceutical University

Principal Investigator

SHIRAKI Kimiyasu  Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Virology, Professor, 医学部, 教授 (50135745)

Co-Investigator(Kenkyū-buntansha) KUROKAWA Masahiko  Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Virology, Associate Professor, 医学部, 助教授(前) (80186527)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsHerpes simplex virus / Viral vector / attenuated vector / neurological function / gene therapy / anterior horn motor neuron / ウイルスベクター / 中枢神経系 / 潜伏感染 / 単純ヘルペスウイルスベクター / 脊髄前角運動細胞 / 神経親和性 / 弱毒ウイルス / 遺伝子発現ベクター
Research Abstract

We have developed a live attenuated HSV-1 vector, βH1, expressing β-galactosidase (β-gal) in the nervous system. Its subcutaneous inoculation led the expression of β-gal activity in neurons of the sensory ganglia innervating the inoculation site for at least 45 days. βH1 was also sufficient to deliver the foreign gene into motor neurons in the bilateral anterior horn of the spinal cord of rats by an intramuscular inoculation and β-gal expression continued for at least 182 days in 90% of motor neurons in the bilateral anterior horn of spinal cord in a wide range. The presence of immunity to HSV was not an obstacle to deliver the transgene in anterior horn motor neurons in the intramuscularly inoculated rats. Furthermore, βH1 inoculation into the right caudate putamen of rats was efficient in expressing β-gal activity not only in the neurons of the inoculation site but also in the area projecting to the inoculation site, where this spread of area was regulated by an anti-HSV agent, ganciclovir. βH1 is originated from HSV-1 HF strain that is attenuated to mice, and expresses β-gal activity in the central nervous system (CNS), especially motor neurons in spinal cord without causing tissue destruction or inflammation. It would be a broad potential vector for gene therapy for familial amyotrophic lateral sclerosis and CNS diseases

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (44 results)

All 2005 2004 2003 2002 2001 Other

All Journal Article (25 results) Publications (19 results)

  • [Journal Article] Growth of herpes simplex virus in epidermal keratinocytes determines cutaneous pathogenicity in mice.2005

    • Author(s)
      Yoshida Y, Li Z-H, Kurokawa M, Kawana T, Imakita M, Shiraki K.
    • Journal Title

      Journal of Mededical Virology 75

      Pages: 421-426

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Growth of herpes simplex virus in epidermal keratinocytes determines cutaneous pathogenicity in mice.2005

    • Author(s)
      Yoshida Y, Li Z-H, Kurohawa M, Kawana T, Imakita M, Shiraki K.
    • Journal Title

      J Med Virol 75

      Pages: 421-426

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparative anti-varicella-zoster virus efficacy of acyclovir and vidarabine.2005

    • Author(s)
      Miwa N, Kurosaki K, Yoshida Y, Kurokawa M, Saito S, Shiraki K.
    • Journal Title

      Antiviral Research 65

      Pages: 49-55

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Suppression of generation and replication of acyclovir-resistant herpes simplex virus by its sensitive virus.2004

    • Author(s)
      Okuda T, Kurokawa K, Matsuo K, Honda M, Niimura M, Shiraki, K.
    • Journal Title

      Journal of Medical Virology 72

      Pages: 112-120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Herpes simplex virus induced death receptor-dependent apoptosis and regression of transplanted human cancers.2004

    • Author(s)
      Kamiyama H, Kurosaki K, Kurimoto M, Katagiri T, Nakamura Y, Kurokawa M, Sato H, Endo S, Shiraki K.
    • Journal Title

      Cancer Science 95

      Pages: 990-998

    • NAID

      10014260689

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Regulation of varicella-zoster virus induced cell-to-cell fusion by the endocytosis competent glycoproteins gH and gE.2004

    • Author(s)
      Pasieka TJ, Shiraki K, Grose C.
    • Journal Title

      Journal of Virology 78

      Pages: 2884-2896

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of suppression of acute herpetic pain by gabapentin and amitriptyline on the incidence of delayed postherpetic pain in mice.2004

    • Author(s)
      Kuraishi Y, Takasaki I, Nojima H, Shiraki K, Takahara H.
    • Journal Title

      Life Sciences 74

      Pages: 2619-2626

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Suppression of generation and replication of acyclovir-resistant herpes simple virus by its sensitive virus.2004

    • Author(s)
      Okuda T, Kurokawa K, Matsuo K, Honda M, Niimura M, Shiraki, K.
    • Journal Title

      J Med Virol 72

      Pages: 112-120

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of suppression of acute herpetic pain by gabapentin and amitriptyline on he incidence of delayed postherpetic pain in mice.2004

    • Author(s)
      Kuraishi Y, Takasaki I, Nojima H, Shiraki K, Takahara H.
    • Journal Title

      Life Sciences 74

      Pages: 2619-2626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Herpes simplex virus induced death receptor-dependent apoptosis and regression of transplanted human cancers.2004

    • Author(s)
      Kamiyama H, Kurosaki K, Kurimoto M, Katagiri T, Nakamura Y, Kurokawa M, Sato H, Endo S, Shiraki K.
    • Journal Title

      Cancer Sci 95

      Pages: 990-998

    • NAID

      10014260689

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of varicella-zoster virus Induced cell-to-cell fusion by the endocytosis competent glycoproteins gH and gE.2004

    • Author(s)
      Pasieka TJ, Shiraki K, Grose C.
    • Journal Title

      J virol 78

      Pages: 2884-2896

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Suppression of generation and replication of acyclovir-resistant herpes simplex virus by its sensitive virus.2004

    • Author(s)
      Okuda T, Kurokawa K, Matsuo K, Honda M, Niimura M, Shiraki, K.
    • Journal Title

      J Medical Virology 72

      Pages: 112-120

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of varicella-zoster virus induced cell-to-cell fusion by the endocytosis competent glycoproteins gH and gE.2004

    • Author(s)
      Pasieka TJ, Shiraki K, Grose C.
    • Journal Title

      J Virology 78

      Pages: 2884-2896

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tropism of varicella-zoster virus to hepatocytes in its pathogenesis and tropism of Oka varicella vaccine to dermal fibroblasts in its attenuation.2003

    • Author(s)
      Shiraki K, Yoshida Y, Asano Y, Yamanishi K, Takahashi M.
    • Journal Title

      Journal of Infectious Diseases 188

      Pages: 1875-1877

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulated transgene delivery by ganciclovir in the brain without physiological alterations by a live attenuated herpes simplex virus vector.2003

    • Author(s)
      Fukuda Y, Yamamura J, Uwano T, Nishijo H, Kurohawa M, Fukuda M, Ono T, Shiraki K.
    • Journal Title

      Neurosci Res 45

      Pages: 233-241

    • NAID

      50000245954

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of cell-mediated and humeral immunity to hepatitis B surface antigen by a novel adjuvant activity of Oka varicella vaccine.2003

    • Author(s)
      Phumiamorn S, Sato H, Kamiyama T, Kurohawa M, Shiraki K.
    • Journal Title

      J Gen virol 84

      Pages: 287-291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tropism of varicella-zoster virus to hepatocytes in its pathogenesis and tropism of Oka varicella vaccine to dermal fibroblasts in its attenuation.2003

    • Author(s)
      Shiraki K, Yoshida Y, Asano Y, Yamanishi K, Takahashi M.
    • Journal Title

      J Infect Dis 188

      Pages: 1875-1877

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of analgesias on delayed postherpetic pain in mice.2002

    • Author(s)
      Takasaki I, Sasaki A, Andoh T, Nojima H, Shiraki K, Kuraishi Y.
    • Journal Title

      Anesthesiology. 96

      Pages: 1168-1174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Analysis of herpes simplex virus isolated from the genital lesions since 1977 in Japan.2001

    • Author(s)
      Hasegawa T, Kawana T, Okuda T, Tsukada T, Horii M, Shiraki K.
    • Journal Title

      J Med Virol 63

      Pages: 57-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection.2001

    • Author(s)
      Tahasaki I., Andoh T., Nojima H., Shiraki K., Kuraishi Y.
    • Journal Title

      J Pharmacol Exp Therapeut 296

      Pages: 270-275

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector.2001

    • Author(s)
      Kamiyama H, Kurimoto M, Yamamura J, Uwano T, Hirashima Y, Kurohawa M, Endo S, Shiraki K.
    • Journal Title

      Gene Therapy 8

      Pages: 1180-1187

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Characterization of the DNA polymerase gene of varicella-zoster viruses resistant to acyclovir.2001

    • Author(s)
      Kamiyama T, Kurohawa M, Shiraki K.
    • Journal Title

      J Gen virol 82

      Pages: 2761-2765

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of long-term low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir-resistance of herpes simplex virus type 2.2001

    • Author(s)
      Honda M, Okuda T, Hasegawa T, Kurohawa M, Shiraki K, Komatsuzaki M, Matsuo K, Niimura M.
    • Journal Title

      Antiviral Chem Chemother 12

      Pages: 243-249

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Varicella-zoster virus gH : gL contains a structure reactive with the anti-human gamma chain of IgG near the glycosylation site.2001

    • Author(s)
      Yokoyama, T., Ayabe, S., Miyagi, H., Sugano, T., Otsu, A., Sato, H., Kageyama, S., Fujii, T., Shiraki, K.
    • Journal Title

      J Gen virol 82

      Pages: 331-334

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Latent gene expression of a live attenuated herpes simplex virus in the spinal cord of rats without electrophysiological alteration.

    • Author(s)
      Kurohawa M, Sato H, Yoshida Y, Kurosahi K, Phumiamorn S, Tamura R, Ono T, Yamamura J, Shiraki K.
    • Journal Title

      (manuscript in preparation)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kurokawa, M., Brown, J., Kagawa, Y., Shiraki, K.: "Cytokine-regulatory activity and therapeutic efficacy of cinnamyl derivatives in endotoxin shock"Eur.J.Pharm.. 474. 283-293 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okuda, T., Kurokawa, M., et al.: "Suppression of generation and replication of acyclovir-resistant herpes simplex virus by a sensitive virus"J.Med.Virol.. 72. 112-120 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukuda, Y., Yamamura, J.et al.: "Regulated transgene delivery by ganciclovir in the brain without physiological alterations by a live attenuated herpes simplex virus vector"Neuroscience Res.. 45. 233-241 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Phumiamorn, S., Sato, H.et al.: "Induction of humoral and cell-mediated immunity to hepatitis B surface antigen by a novel aduvant activity of Oka varicella vaccine"J.Gen.Virol.. 84. 287-291 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lipipun V., Kurokawa M.et al.: "Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo"Antiviral Res.. 60. 175-180 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato, H., Yamamura, J.et al.: "Superiority of varicella skin test antigen over purified varicella-zoster virus glycoproteins in monitoring booster response to Oka varicella vaccine"Vaccine. 22. 15-20 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shiraki K, Yoshida Y, Asano Y, Yamanishi K, Takahashi M.: "Tropism of varicella-zoster virus to hepatocytes in its pathogenesis and tropism of Oka varicella vaccine to dermal fibroblasts in its attenuation"J.Infect.Dis.. 188. 1875-1877 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukuda Y et al.: "Regulated transgene delivery by ganciclovir in the brain without physiological alterations by a live attenuated herpes simplex virus vector"Neuroscience Research. 45. 233-241 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Phumiamorn S et al.: "Induction of cell-mediated and humoral immunity to hepatitis B surface antigen by a novel adjuvant activity of Oka varicella vaccine"Journal of General Virology. 84. 287-291 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuji T et al.: "Induction of cellular immunity to varicella-zoster virus glycoproteins tested with pernasal co-administration of Escherichia coli enterotoxin in mice"Journal of Medical Virology. 69. 451-458 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takasaki I et al.: "Effects of analgesics on delayed postherpetic pain in mice"Anesthesiology. 96. 1168-1174 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurokawa M et al.: "Effect of interleukin-12 level augmented by Kakkon-to, a herbal medicine, in the early stage of influenza infection on its alleviation"Antiviral Research. 56. 183-188 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furuta Y et al.: "In vitro and in vivo activities of anti-influenza viral compound T-705"Antimicrobial Agents & Chemotherapy. 46. 977-981 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kamiyama et al.: "Effect of immunity on gene delivery into anterior horn motor neurons by live attenuated herpes simplex virus vector."Gene Therapy. 8. 1180-1187 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takasaki et al.: "Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection."Journal of Pharmcology and Experimental Therapeutics. 296. 270-275 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shiraki et al.: "Construction of Oka varicella vaccine expressing human immunodeficiency virus env antigen."Journal of Medical Virology. 64. 96-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokoyama et al.: "Varicella-zoster virus gH : gL contains a structure reactive with the anti-human gamma chain of IgG near the glycosylation site."Journal of General Virology. 82. 331-334 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamiyama et al.: "Characterization of the DNA polymerase gene of varicella-zoster viruses resistant to acyclovir"Journal of General Virology. 82. 2761-2765 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurokawa et al.: "Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo."Journal of Pharmcology and Experimental Therapeutics. 297. 372-379 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi