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2011 Fiscal Year Final Research Report

Transcriptional regulation of herpesviruses dependent on the viral DNA replication

Research Project

  • PDF
Project/Area Number 21590524
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionGunma University (2011)
Aichi Cancer Center Research Institute (2009-2010)

Principal Investigator

ISOMURA Hiroki  群馬大学, 大学院・医学系研究科, 教授 (20294415)

Project Period (FY) 2009 – 2011
Keywordsヒトサイトメガロウイルス
Research Abstract

The regulation of human cytomegalovirus (HCMV) late gene expression by viral proteins is poorly understood. HCMV open reading frames (ORFs) UL79,-87, and-95 encode proteins with homology to late gene transcription factors of murine gammaherpesvirus 68 ORFs 18, 24, and 34, respectively. To determine whether these HCMV proteins are also essential for late gene transcription of a betaherpesvirus, we mutated HCMV ORFs UL79,-87, and-95. Cells were infected with the recombinant viruses at high and low multiplicities of infection (MOIs). While viral DNA was detected with the recombinant viruses, infectious virus was not detected unless the wild-type viral proteins were expressed in trans. At a high MOI, mutation of ORF UL79,-87, or-95 had no effect on the level of major immediate-early (MIE) gene expression or viral DNA replication, but late viral gene expression from the UL44,-75, and-99 ORFs was not detected. At a low MOI, preexpression of UL79 or-87, but not UL95, in human fibroblast cells negatively affected the level of MIE viral gene expression and viral DNA replication. The products of ORFs UL79,-87, and-95 were expressed as early viral proteins and recruited to prereplication complexes (pre-RCs), along with UL44, before the initiation of viral DNA replication. All three HCMV ORFs are indispensable for late viral gene expression and viral growth.

  • Research Products

    (11 results)

All 2011 2010 2009 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] The human cytomegalovirus gene products essential for late viral gene expression assemble into pre-replication complexes before viral DNA replication2011

    • Author(s)
      Isomura H, Stinski MF, Murata T, Yamashita Y, Kanda T, Toyokuni S, Tsurumi T
    • Journal Title

      J Virol

      Volume: 85 Pages: 6629-6644

    • Peer Reviewed
  • [Journal Article] The human cytomegalovirus UL76 gene regulates the level of expression of the UL77gene2010

    • Author(s)
      Isomura H, Stinski MF, Murata T, Nakayama S, Chiba S, Akatsuka Y, Kanda T, Tsurumi T
    • Journal Title

      PLoS One

      Volume: 5 Pages: e11901

    • Peer Reviewed
  • [Presentation] The human cytomegalovirus gene products essential for late viral gene expression assemble into pre-replication complexes before viral DNA replication2011

    • Author(s)
      Isomura H., Tsurumi T
    • Organizer
      International Union of Microbiological Societies Congress (IUMS)
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      2011-09-15
  • [Presentation] Human cytomegalovirus genes required for late viral gene expression and assembly into pre-replication complexes before viral DNA replication2011

    • Author(s)
      Isomura H., Tsurumi T
    • Organizer
      13th CMV / BetaHerpesvirus Workshop
    • Place of Presentation
      Nuremberg, Germany
    • Year and Date
      2011-05-16
  • [Presentation] Human Cytomegalovirus Late Transactivators Recruited to the Replication Compartments2010

    • Author(s)
      Isomura H., Stinski M.F., Murata T., Kanda T., Tsurumi T
    • Organizer
      35th International Herpesvirus Workshop
    • Place of Presentation
      Salt Lake City, Utah, USA
    • Year and Date
      2010-07-24
  • [Presentation] Human cytomegalovirus UL76 gene regulates the level of expression of the UL77 gene2009

    • Author(s)
      Isomura H., Stinski M.F., Nakayama S., Chiba S., Akatsuka Y., Kanda T., Tsurumi T
    • Organizer
      14th International Conferences on the Immunobiology and Prophylaxis of Human Herpesvirus Infections
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2009-10-06
  • [Book] ヒトサイトメガロウイルス.松島綱治編,分子予防環境医学2010

    • Author(s)
      磯村寛樹
    • Total Pages
      218-224
    • Publisher
      東京:本の泉社
  • [Book] DNA polymerase processivity factor of human cytomegalovirus may be a key molecule for molecular coupling of viral DNA replication to transcription. Edited by Jelena Kusic, DNA Replication/Book 2, ISBN

    • Author(s)
      Isomura H
    • Total Pages
      978
    • Publisher
      Croatia, InTech-Open Acess Publisher
  • [Remarks]

    • URL

      http://www.med.gunma-u.ac.jp/med-organization/envmed/envmed-defense/153.html/

  • [Patent(Industrial Property Rights)] ヒトの体内では増殖不可能な弱毒性ヒトサイトメガロウィルス株の作成2011

    • Inventor(s)
      磯村寛樹, 鶴見達也
    • Industrial Property Rights Holder
      愛知県
    • Industrial Property Number
      特願、2011-14548
    • Filing Date
      2011-01-26
  • [Patent(Industrial Property Rights)] ヒトサイトメガロウイルスの複製制御2010

    • Inventor(s)
      磯村寛樹, 鶴見達也
    • Industrial Property Rights Holder
      愛知県
    • Industrial Property Number
      特許、第441640号
    • Acquisition Date
      2010-01-22

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Published: 2013-07-31  

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