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2012 Fiscal Year Final Research Report

Study on cytomegalovirus: cell tropism, pathogenesis, and induction of protective antibodies.

Research Project

  • PDF
Project/Area Number 22590426
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

INOUE Naoki  国立感染症研究所, ウイルス第一部, 室長 (90183186)

Research Collaborator HASHIMOTO Kaede  国立感染症研究所, ウイルス第一部, 研究生
FUKUCHI Saki  国立感染症研究所, ウイルス第一部, 研究生
FUKUI Yoshiko  国立感染症研究所, ウイルス第一部, 非常勤職員
TSUDA Mihoko  国立感染症研究所, ウイルス第一部, 非常勤職員
Project Period (FY) 2010 – 2012
Keywordsサイトメガロウイルス / モルモット / 感染防御 / 糖蛋白 / 細胞指向性
Research Abstract

In contrast to murine and rat CMVs, guinea pig CMV (GPCMV) crosses the placenta and causes infection in utero, which makes GPCMV animal models useful for studies on the mechanisms of transplacental transmission of CMV. Previously, we reported that the GPCMV stock purchased from the ATCC contained two types of strains, one containing and the other lacking a 1.6 kb locus that encodes human CMV UL128 and UL130 homologs, GP129 and GP131, and that the 1.6 kb locus was required for efficient viral growth in animals but not in cell culture. HCMV UL128/130/131A form a pentamer complex with gH/gL and play a role in the endothelial/epithelial-tropism. In this study, we constructed a BAC containing a GPCMV genome, the virus from which grew normally in guinea pig fibroblast cells GPL. Using the RedET recombination system for BAC, mutations were introduced into each of GP129, GP131, and GP133 ORFs. Although all mutants grew in GPL and epithelial cell line GPC-16 at the level similar to a virus derived from the BAC with the wild-type sequence, they could not infect monocytes/ macrophages. GPCMV was transmittable to fibroblast from infected macrophages by co-culturing. Since macrophages play an important role in dissemination of virus to the organs, the macrophage tropism may associate with efficient viral growth in vivo.

  • Research Products

    (14 results)

All 2013 2012 2011 2010

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (9 results)

  • [Journal Article] Effects of immunization of pregnant guinea pigs with guinea pig cytomegalovirus glycoprotein B on viral spread in the placenta.2013

    • Author(s)
      Hashimoto K, Yamada S, Katano H, Fukuchi S, Sato Y, Kato M, Yamaguchi T, Moriishi K, Inoue N
    • Journal Title

      Vaccine

      Volume: 31 Pages: 3199-205

    • DOI

      DOI:10.1016/j.vaccine.2013.04.078

    • Peer Reviewed
  • [Journal Article] Cytomegalovirus impairs CTB-induced lymph- angiogenesis and vascular remodeling in an in vivo human placentation model.2012

    • Author(s)
      Tabata T, Petitt M, Fang-Hoover J, Rivera J, Nozawa N, Shiboski S, Inoue N, Pereira L
    • Journal Title

      Am. J. Pathol.

      Volume: 181 Pages: 1540-59

    • DOI

      DOI:10.1016/j.ajpath.2012.08.003

    • Peer Reviewed
  • [Journal Article] novel real-time PCR method for the determination and quantification of each cytomegalovirus (CMV) gH- subtype in clinical samples2012

    • Author(s)
      Ikuta K, Ishioka K, Sato Y, Imamura T, Asano K, Koyano S, Inoue N, Suzutani T
    • Journal Title

      J. Clin. Microbiol

      Volume: 50 Pages: 499-501

    • DOI

      DOI:10.1128/JCM.06032-11

    • Peer Reviewed
  • [Journal Article] The lack of antibodies against the AD2 epitope of cytomegalovirus (CMV) glycol- protein B (gB) is associated with CMV disease after renal transplantation in recipients having gH serotypes same as their donors.2011

    • Author(s)
      Ishibashi K, Tokumoto T, Shirakawa H, Hashimoto K, Ikuta K, Kushida N, Yanagida T, Shishido K, Aikawa K, Toma H, Inoue N, Yamaguchi O, Tanabe K, Suzutani T
    • Journal Title

      Transplant. Infect. Dis.

      Volume: 13 Pages: 318- 28

    • DOI

      DOI:10.1111/j.1399-3062.2010.00563.x

    • Peer Reviewed
  • [Journal Article] Re-evaluation of guinea pig cytomegalovirus complete genome sequence.2011

    • Author(s)
      Kanai K, Yamada S, Yamamoto Y, Fukui Y, Kurane I, Inoue N
    • Journal Title

      J. Gen. Virol.

      Volume: 92 Pages: 1005-20

    • DOI

      DOI:10.1099/vir.0.027789-0

    • Peer Reviewed
  • [Presentation] モルモット妊娠動物モデルを用いたサイトメガロウイルス糖蛋白Bサブユニットワクチンの効果機序の解析2012

    • Author(s)
      橋本楓、山田壮一、片野晴隆、福地早希、佐藤由子、森石恆司、井上直樹
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20121100
  • [Presentation] モルモットサイトメガロウイルス(GPCMV)を用いた先天性感染病態の解析2012

    • Author(s)
      福地早希, 山田壮一, 橋本楓, 片野晴隆, 佐藤由子, 森石恆司, 井上直樹
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20121100
  • [Presentation] Immunization of pregnant guinea pigs with glycoprotein B (gB).2012

    • Author(s)
      Hashimoto K, Yamada S, Fukuchi S, Katano H, Sato Y, Kato M, Moriishi K, Inoue N
    • Organizer
      4th Congenital CMV Conference/the International Betaherpesvirus Workshop
    • Place of Presentation
      San Francisco
    • Year and Date
      20121000
  • [Presentation] Congenital cytomegalovirus infection identified in pregnancies complicated by idiopathic intrauterine growth restriction.2012

    • Author(s)
      Tabata T, Petitt M, Fang-Hoover J, Rivera J, Nozawa N, Shiboski S, Inoue N, Pereira L.
    • Organizer
      4th Congenital CMV Conference & 14th International CMV/beta-herpesvirus Workshop
    • Place of Presentation
      San Francisco
    • Year and Date
      20121000
  • [Presentation] モルモット感染動物モデルを用いたサイトメガロウィルスワクチン開発の基礎検討2011

    • Author(s)
      橋本楓、井上直樹
    • Organizer
      第15回日本ワクチン学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20111200
  • [Presentation] Characterization of human cytomegalovirus UL136 gene product.2011

    • Author(s)
      Huanan Kiao, Jung-Hyun Lee, Naoki Inoue, Kenji Miyado, Shigeyoshi Fujiwara
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo
    • Year and Date
      20110900
  • [Presentation] A genotypic and serologic study of cytomegalovirus (CMV) reinfection in mothers and neonates with congenital CMV infection in Japan.2011

    • Author(s)
      Kazufumi Ikuta, Ken Ishioka, Takashi Imamura, Kimisato Asano, Tetsushi Yoshikawa, Hiroyuki Moriuchi, Shigeyoshi Fujiwara, Takahiko Kubo, Shin Koyano, Naoki Inoue, Tatsuo Suzutani
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo
    • Year and Date
      20110900
  • [Presentation] ヒトサイトメガロウイルスUL136領域に見出された新規遺伝子産物2010

    • Author(s)
      廖華南、Jung-Hyun Lee, 井上直樹、宮戸健二、藤原成悦、中村浩幸
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      20101100
  • [Presentation] In vivoで増殖可能なGuinea pig (GPCMV)のゲノム配列の解析2010

    • Author(s)
      金井亨輔、山田壮一、山本由美子、福井良子、倉根一郎、井上直樹
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      20101100

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Published: 2014-08-29   Modified: 2014-09-16  

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