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Changes of cell cycle distribution and nuclear structure in NK cells by EBV infection

Research Project

Project/Area Number 14570997
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJuntendo University

Principal Investigator

SUGIMOTO Koichi  Juntendo Univ School of Medicine, Division of Hematology, Department of Internal Medicine, Assistant Professor, 医学部, 講師 (50281358)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsEGFP-EBV / NK cell / Latent infection / G2 arrest / Latency type I / Genomic instability / Resistance to chemotherapy / 抗癌剤への耐性 / EBウイルス / GFP蛋白質 / 多核細胞 / cdc2 / cdc25C / actin / α-tubulin
Research Abstract

Although considerable part of natural killer (NK) cell neoplasms possess EBV genome, there has been no direct evidence that EBV infects human NK cells in vitro. In this study, we demonstrated EBV entry into the NK cells using enhanced green fluorescence (EGFP)-containing recombinant EBV. After 48 hr, about 30% of NK cell lines and more than 40% of normal peripheral blood NK cells were positive for EGFP signal. In situ hybridization for EBNAs and BHLFs showed that latent and lytic infections coexisted at the early phase of EBV infection. NK cells in latent but not lytic EBV infection tended to show a bizzare and giant shape. Cdc2, cyclin B, and Cdc25C, which are important for G2/M transition, increased in protein levels and partially migrated to the nucleus though their activation was inhibited. Flow cytometric analysis showed mainly G2 arrest in EBV-infected NK cells. Although nuclear distribution of PML, SC35, and HP1 was unchanged, cyto- and nuclear-skeletons made of actin, tubulin and lamin has apparently rearranged and abnormalities of centrosome numbers were detected. We established eight EBV-carrying clones, which showed both latency types I and II. Both of them are recognized in EBV-associated NK-cell neoplasms. The cell size became larger and the frequency of micronuclei formation, a hallmark of genomic instability, increased in EBV-carrying NKL clones. Furthermore, these clones were resistant to various chemotherapeutic agents and cell dilution compared to the parent NK cell lines.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (8 results)

All 2004 Other

All Journal Article (2 results) Publications (6 results)

  • [Journal Article] Epstein-Barr virus infection of human natural killer cell lines and peripheral blood natural killer cells.2004

    • Author(s)
      Isobe Y, Sugimoto K, et al.
    • Journal Title

      Cancer Research 64

      Pages: 2167-2174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Epstein-Barr virus infection of human natural killer cell lines and peripheral blood natural killer cells.2004

    • Author(s)
      Isobe Y, Sugimoto K, Yang L, Tamayose K, Egashira M, Kaneko T, Takada K, Oshimi K
    • Journal Title

      Cancer Res 64

      Pages: 2167-2174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 杉本耕一: "Low-dose doxorubicin-induced necrosis in Jurkat cells and its acceleration and conversion to apoptosis by antioxidants"British Journal of Haematology. 118. 229-238 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉本耕一: "More than 13 years-lasting hypereosinophilia associated with clonal CD3-CD4+ lymphocytosis of Th2/Th0-type"International Journal of Hematology. 75. 281-284 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 玉寄謙治: "CD3-negative, CD20-positive T-cell prolymphocytic leukemia : case report and review of the literature"American Journal of Hematology. 71. 331-335 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 杉本耕一: "Low-dose doxorubicin-induced necrosis in Jurkat cells and its acceleration and conversion to apoptosis by antioxidants"British Journal of Haematology. 118. 229-238 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 杉本耕一: "More than 13 years-lasting hypereosinophilia associated with clonal CD3-CD4+ lymphocytosis of Th2/Th0-type"International Journal of Hematology. 75. 281-284 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 玉寄謙治: "CD3-negative, CD20-positive T-cell prolymphocytic leukemia : case report and review of the literature"American Journal of Hematology. 71. 331-335 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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