In Vitro Behavior of Hepatitis C Virus JFH-1 Strains with Mutations Emerged after Passage in Chimpanzees

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590868
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KATO Takanobu 国立感染症研究所, ウイルス第二部, 室長 (20333370)
• Project Period (FY): 2009 – 2011
• Keywords: HCV / 慢性化 / ウイルス培養 / 感染実験 / チンパンジー

Research Abstract

Although JFH-1 replicates efficiently and produces infectious virus in cell culture, the relationship between in vitro phenotype and in vivo pathogenesis is still unclear. We synthesized the full-genome JFH-1 constructs with mutations detected in chimpanzees and assessed effects of these mutations on viral production in vitro. Higher virus assembly and lower replication capacity of JFH-1 with these mutations were observed. The control of viral production such as replicati on, assembly and secretion by specific mutations may be a key of viral strategy to evade host defense mechanisms.

Research Products

• [Journal Article] Role of the Endoplasmic Reticulum-associated Degradation(ERAD) Pathway in Degradation of Hepatitis C Virus Envelope Proteins and Production of Virus Particles (2011)
  • Author(s): Saeed M, Suzuki R, Watanabe N, Masaki T, Tomonaga M, Muhammad A, Kato T, Matsuura Y, Watanabe H, Wakita T, Suzuki T
  • Journal Title: J Biol Chem Volume: 286 Pages: 37264-37273
• [Journal Article] In vivo adaptation of hepatitis C virus in chimpanzees for efficient virus production and evasion of apoptosis (2011)
  • Author(s): Saeed M, Shiina M, Date T, Akazawa D, Watanabe N, Murayama A, Suzuki T, Watanabe H, Hiraga N, Imamura M, Chayama K, Choi Y, Krawczynski K, Liang TJ, Wakita T, Kato T
  • Journal Title: Hepatology Volume: 54 Pages: 425-433
• [Journal Article] Development of recombinant hepatitis C virus with NS5A from strains of genotypes 1 and 2 (2011)
  • Author(s): Okamoto Y, Masaki T, Murayama A, Munakata T, Nomoto A, Nakamoto S, Yokosuka O, Watanabe H, Wakita T, Kato T
  • Journal Title: Biochem Biophys Res Commun Volume: 410 Pages: 404-409
• [Journal Article] Studies on virus kinetics using infectious fluorescence-tagged hepatitis C virus cell culture (2011)
  • Author(s): Yamamoto M, Sakamoto N, Nakamura T, Itsui Y, Nakagawa M, Nishimura-Sakurai Y, Kakinuma S, Azuma S, Tsuchiya K, Kato T, Wakita T, Watanabe M
  • Journal Title: Hepatol Res Volume: 41 Pages: 258-269
• [Journal Article] Biological properties of purified recombinant HCV particles with an epitope-tagged envelope (2010)
  • Author(s): Takahashi H, Akazawa D, Kato T, Date T, Shirakura M, Nakamura N, Mochizuki H, Tanaka-Kaneko K, Sata T, Tan aka Y, Mizokami M, Suzuki T, Wakita T
  • Journal Title: Biochem Biophys Res Commun Volume: 395 Pages: 565-571
• [Journal Article] RNA polymerase activity and specific RNA structure are required for efficient HCV replication in cultured cells (2010)
  • Author(s): Murayama A, Weng L, Date T, Akazawa D, Tian X, Suzuki T, Kato T, Tanaka Y, Mizokami M, Wakita T, Toyoda T
  • Journal Title: PLoS Pathog Volume: 6 Pages: e1000885
• [Presentation] HCVの増殖適応変異とその意義 (2010)
  • Author(s): 加藤孝宣,岡本有加,村山麻子,政木隆博,脇田隆字
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20101107-09
• [Presentation] C型肝炎ウイルスJFH-1株患者血清のチンパンジーへの感染実験 (2010)
  • Author(s): 加藤孝宣, Saeed Mohsan,脇田隆字
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20101107-09
• [Presentation] Specific RNA structures and mutations implicated for HCV RNA replication and virus particle formation in cultured cells (2009)
  • Author(s): Asako Murayama, Tomoko Date, Daisuke Akazawa, Takanobu Kato, Tetsuro Suzuki, and Takaji Wakita
  • Organizer: The Liver Meeting 2009, AASLD's 60th Annual Meeting
  • Place of Presentation: Boston, MA
  • Year and Date: 20091030-1103
• [Presentation] C型肝炎ウイルスの複製増殖に関与するウイルス遺伝子変異および遺伝子構造の解析 (2009)
  • Author(s): 村山麻子,伊達朋子,赤澤大輔,加藤孝宣,鈴木哲朗,豊田哲也,脇田隆字
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20091025-27
• [Presentation] In vitro behavior of hepatitis C virus JFH-1 strains with mutations emerged after passage in chimpanzees (2009)
  • Author(s): Mohsan Saeed, Takanobu Kato, Youkyung Choi, Krzyaztof Krawczynski, Jake Liang, Takaji Wakita
  • Organizer: 16^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Nice, France
  • Year and Date: 20091003-07
• [Presentation] Dynamic profile of gene expression in the liver during hepatitis C virus(HCV) JFH1 infection in chimpanzees (2009)
  • Author(s): Youkyung Choi, Takanobu Kato, Takaji Wakita, Jake Liang, Krzyaztof Krawczynski
  • Organizer: 16^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Nice, France
  • Year and Date: 20091003-07
• [Presentation] C型肝炎ウイルスの生体内での感染様式と培養細胞での増殖能 (2009)
  • Author(s): 加藤孝宣,伊達朋子,脇田隆字
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 20090604-05
• [Presentation] C型肝炎ウイルスの複製増殖に関与するウイルス遺伝子領域の検討 (2009)
  • Author(s): 村山麻子,加藤孝宣,脇田隆字
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 20090604-05