Costraction of full-length lymphotropic HCV strain and immunopathogenesis of HCV lymphotropism

• Project/Area Number: 21790642
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: KONDO Yasuteru Tohoku University, 病院, 医員 (70455822)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: C型肝炎ウイルス / リンパ指向性HCV / T細胞 / HCV / Lymphotropism / Th17 / 自己免疫疾患 / ナイーブT細胞 / リンパ指向性 / 肝外疾患 / CD4

Research Abstract

It was shown that lymphotropic HCV (SB-HCV strain) derived from B cell lymphoma could not only replicate in lymphoma-cell-lines but also in primary human lymphocyte especially B cells and CD45RA+RO-naive T cells. SB-HCV strain could infect naive CD4+ cells and suppress the activity of proliferation. We have found that HCV-core protein is responsible protein that could block STAT-1 signaling.

Research Products

• [Journal Article] Dysfunction of Immune Systems and Host Genetic Factors in Hepatitis C Virus Infection with Persistent Normal ALT. (2011)
  • Author(s): Kondo Y, Ueno Y, Shimosegawa T.
  • Journal Title: Hepatitis Research and Treatment in press
  • Peer Reviewed
• [Journal Article] Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients : influence of hepatitis B virus enotype and resistance mutation pattern. (2011)
  • Author(s): Inoue J, Ueno Y, Wakui Y, Niitsuma H, Fukushima K, Yamagiwa Y, Shiina M, Kondo Y, Kakazu E, Tamai K, Obara N, Iwasaki T, Shimosegawa T.
  • Journal Title: J Viral Hepat. 18(3) Pages: 206-215
  • Peer Reviewed
• [Journal Article] Lymphotropic HCV strain can infect human primary naive CD4(+) cells and affect their proliferation and IFN-gamma secretion activity. (2011)
  • Author(s): Kondo Y, Ueno Y, Kakazu E, Kobayashi K, Shiina M, Tamai K, Machida K, Inoue J, Wakui Y, Fukushima K, Obara N, Kimura O, Shimosegawa T.
  • Journal Title: Journal of Gastroenterology Volume: 46 Pages: 232-41
  • Peer Reviewed
• [Journal Article] Lymphotropic HCV strain can infect human primary naive CD4(+) cells and affect their proliferation and IFN-gamma secretion activity. (2010)
  • Author(s): Kondo Y, Ueno Y, et al.
  • Journal Title: J Gastroenterol. Pages: 232-241
  • Peer Reviewed
• [Journal Article] Characterization of the epithelial cell adhesion molecule (EpCAM) cell population in hepatocellular carcinoma cell lines. (2010)
  • Author(s): Kimura O, Takahashi T, Ishii N, Inoue Y, Ueno Y, Kogure T, Fukushima K, Shiina M, Yamagiwa Y, Kondo Y, Inoue J, Kakazu E, Iwasaki T, Kawagishi N, Shimosegawa T, Sugamura K.
  • Journal Title: Cancer Sci. Pages: 2145-2155
  • NAID: 10027832222
  • Peer Reviewed
• [Journal Article] Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. (2010)
  • Author(s): Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y, Inoue J, Shiina M, Fukushima K, Hoshino T, Sano K, Ueno Y, Shimosegawa T, Sugamura K.
  • Journal Title: Biochem Biophys Res Commun. 399(3) Pages: 384-390
  • Peer Reviewed
• [Journal Article] Hepatitis B virus-replication could enhance Tregs activity by producing sHSP60 from hepatocyte. (2010)
  • Author(s): Kondo Y, Ueno Y, Kobayashi K, et al.
  • Journal Title: J Infect Dis. 202(2) Pages: 202-213
  • Peer Reviewed
• [Journal Article] Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. (2010)
  • Author(s): Obara N, Fukushima K, Ueno Y, Wakui Y, Kimura O, Tamai K, Kakazu E, Inoue J, Kondo Y, Ogawa N, Sato K, Tsuduki T, Ishida K, Shimosegawa T.
  • Journal Title: J Hepatol. 53(2) Pages: 326-334
  • Peer Reviewed
• [Journal Article] Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone. (2010)
  • Author(s): Wakui Y, Inoue J, Ueno Y, Fukushima K, Kondo Y, Kakazu E, Obara N, Kimura O, Shimosegawa T.
  • Journal Title: Biochem Biophys Res Commun. 396(2) Pages: 508-514
  • Peer Reviewed
• [Journal Article] Peg-IFN+RBV併用長期投与の可能性 (2010)
  • Author(s): 近藤泰輝、上野義之、下瀬川徹
  • Journal Title: 肝胆膵 (61) Pages: 90-96
• [Journal Article] HBV複製ストレスと細胞性免疫能の関係(解説) (2010)
  • Author(s): 近藤泰輝, 上野義之, 下瀬川徹
  • Journal Title: Minophagen Medical Review(0388-4783) 55巻2号 Pages: 163-165
• [Journal Article] HCV感染における小胞輸送経路ESCRTの役割(原著論文) (2010)
  • Author(s): 玉井恵一, 上野義之, 涌井祐太, 小原範之, 嘉数英二, 井上淳, 近藤泰輝, 山極洋子, 椎名正明, 福島耕治, 岩崎隆雄, 下瀬川徹
  • Journal Title: Source:消化器と免疫 46号 Pages: 206-210
• [Journal Article] HBV複製ストレスと細胞性免疫能の関係 (2010)
  • Author(s): 近藤泰輝、上野義之、下瀬川徹
  • Journal Title: Minophagen Medical Review Volume: 55(2) Pages: 163-165
• [Journal Article] Peg-IFN/RBV併用長期投与の可能性 (2010)
  • Author(s): 近藤泰輝、上野義之、下瀬川徹
  • Journal Title: 肝胆膵 Volume: 61 Pages: 90-96
• [Journal Article] Hepatitis B virus-replication could enhance Tregs activity by producing sHSP60 from hepatocyte (2010)
  • Author(s): Kondo Y, Ueno Y, Kobayashi K, Kakazu E, Shiina M, Inoue J, et al.
  • Journal Title: Journal of Infectious Diseases (未定, 印刷中)
  • Peer Reviewed
• [Journal Article] Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis. (2009)
  • Author(s): Kakazu E, Ueno Y, Kondo Y, Fukushima K, Shiina M, Inoue J, Tamai K, Ninomiya M, Shimosegawa T.
  • Journal Title: Hepatology. 50(6) Pages: 1936-1945
  • Peer Reviewed
• [Journal Article] Enhanced intracellular retention of a hepatitis B virus strain associated with fulminant hepatitis. (2009)
  • Author(s): Inoue J, Ueno Y, Nagasaki F, Wakui Y, Kondo Y, Fukushima K, Niitsuma H, Shimosegawa T.
  • Journal Title: Virology. 395(2) Pages: 202-209
  • Peer Reviewed
• [Journal Article] Immunopathogenesis of hepatitis B persistent infection : implications for immunotherapeutic strategies (2009)
  • Author(s): Kondo Y, Ueno Y, Shimosegawa T.
  • Journal Title: Clinical Journal of Gastroenterology 2(2) Pages: 71-79
  • Peer Reviewed
• [Journal Article] A novel third generation bisphosphonate (2009)
  • Author(s): Kogure T, Ueno Y, Osamu K, Kondo Y, Inoue J, Fukushima K, Iwasaki T, Shimosegawa T.
  • Journal Title: minodronate (YM529) prevented proliferation and migration of hepatocellular carcinoma cells through inhibition of mevalonate pathway. 39(5) Pages: 479-489
  • Peer Reviewed
• [Journal Article] Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan. (2009)
  • Author(s): Inoue J, Ueno Y, Nagasaki F, Akahane T, Fukushima K, Kogure T, Kondo Y, Kakazu E, Tamai K, Kido O, Nakagome Y, Ninomiya M, Obara N, Wakui Y, Takahashi M, Okamoto H, Shimosegawa T.
  • Journal Title: J Gastroenterol. 44(4) Pages: 329-337
  • NAID: 10025174367
  • Peer Reviewed
• [Journal Article] Hepatitis C virus infection of T cells inhibits proliferation and enhances FAS-mediated apoptosis of T cells by down-regulating CD44v6 expression. (2009)
  • Author(s): Inoue J, Ueno Y, Nagasaki F, Akahane T, Fukushima K, Kogure T, Kondo Y, Kakazu E, Tamai K, Kido O, Nakagome Y, Ninomiya M, Obara N, Wakui Y, Takahashi M, Okamoto H, Shimosegawa T.
  • Journal Title: J Infect Dis. 199(5) Pages: 726-736
  • Peer Reviewed
• [Journal Article] 【肝硬変・肝癌の栄養代謝異常とその対策】肝硬変・肝癌の栄養代謝異常とその対策「非代償性肝硬変におけるアミノ酸imbalanceが免疫機構に及ぼす影響」 (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 下瀬川徹
  • Journal Title: 消化器科(0289-8756) 49巻2号 Pages: 190-196
• [Journal Article] 非代償性肝硬変で出現する血漿アミノ酸不均衡は樹状細胞の成熟化を抑制する (2009)
  • Author(s): 嘉数英二, 上野義之, 近藤泰輝, 福島耕治, 椎名正明, 井上淳, 玉井恵一, 二宮匡史, 下瀬川徹
  • Journal Title: 東北医学雑誌(0040-8700) 121巻1号 Pages: 98-100
  • NAID: 10026082987
• [Journal Article] HBV感染の際に肝細胞より産生されるsHSP60のTregs活性化における意義 (2009)
  • Author(s): 近藤泰輝, et al.
  • Journal Title: Minophagen Medical Review(0388-4783) 54巻2号 Pages: 137-139
• [Journal Article] Hepatitis C virus infection of T cells inhibits proliferation and enhances FAS-mediated apoptosis of T cells by down-regulating CD44v6 expression (2009)
  • Author(s): Kondo Y, Machida K, Liu M, Ueno Y, Kobayashi K, Wakita T, et al.
  • Journal Title: Journal of Infectious Diseases 199(5) Pages: 726-36
  • Peer Reviewed
• [Journal Article] Immunopathogenesis of hepatitis B persistent infection : implications for immunot herapeutic strategies (2009)
  • Author(s): Kondo Y, Ueno Y, Shimosegawa T.
  • Journal Title: Clinical Journal of Gastroenterology 2(2) Pages: 71-79
  • Peer Reviewed
• [Presentation] Immunological Response of HBV/HCV Co-infected Patients (2010)
  • Author(s): Kondo Y, et al.
  • Organizer: APASL STC HCV
  • Place of Presentation: 千葉-幕張
  • Year and Date: 2010-12-18
• [Presentation] Immunological Response of HBV/HCV Co-infected Patients (2010)
  • Author(s): Yasuteru Kondo, 他
  • Organizer: APASL single topic conference
  • Place of Presentation: 千葉
  • Year and Date: 2010-12-17
• [Presentation] 病態解明と治療への応用HBV複製を制御するための免疫病態解析 (2010)
  • Author(s): 近藤泰輝, 上野義之, 下瀬川徹
  • Organizer: 日本肝臓学会 東部会 シンポジウム ウイルス肝炎における免疫応答の研究
  • Place of Presentation: 東京
  • Year and Date: 2010-12-02
• [Presentation] シンポジウム2:肝疾患と免疫 HBV複製を制御するための免疫病態解析 (2010)
  • Author(s): 近藤泰輝, 他
  • Organizer: 肝臓学会東部会
  • Place of Presentation: 東京
  • Year and Date: 2010-12-02
• [Presentation] Analysis of chemokines derived from HBV-replicated hepatocellular carcinoma and inframed hepatocyte (2010)
  • Author(s): Kondo Y, et al.
  • Organizer: AASLD
  • Place of Presentation: ボストン
  • Year and Date: 2010-11-01
• [Presentation] Analysis of chemokines derived from HBV-replicated hepatocellular carcinoma and inframed hepatocyte (2010)
  • Author(s): Yasuteru Kondo, 他
  • Organizer: AASLD annual meeting
  • Place of Presentation: 米国 ボストン
  • Year and Date: 2010-11-01
• [Presentation] Drug FreeにてHBV複製をコントロールするための免疫病態解析 (2010)
  • Author(s): 近藤泰輝, 上野義之, 下瀬川徹
  • Organizer: 日本肝臓学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-13
• [Presentation] Possible Pathogenesis of Autoimmune Disease in Chronic HCV Infection (2010)
  • Author(s): Kondo Y, et al.
  • Organizer: Relationship between Lymphotropic HCV and Th17 International meeting on Hepatitis C virus and related virus
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-16
• [Presentation] Possible Pathogenesis of Autoimmune, Disease in Chronic HCV Infection : Relationship between Lymphotropic HCV and Th17 (2010)
  • Author(s): Yasuteru Kondo, 他
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-16
• [Presentation] HCVウイルス感染とTh17分化誘導 (2010)
  • Author(s): 近藤泰輝, et al.
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] シンポジウム:C型肝炎 ウイルス感染の分子免疫機構HCV複製がT細胞内免疫シグナルに及ぼす影響と病態の関わり (2010)
  • Author(s): 近藤泰輝、上野義之、下瀬川徹
  • Organizer: 日本消化器病学会総会2010
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-23
• [Presentation] シンポジウム7:C型肝炎:ウイルス感染の分子免疫機構HCV複製がT細胞内免疫シグナルに及ぼす影響と病態の関わり (2010)
  • Author(s): 近藤泰輝、上野義之、下瀬川徹
  • Organizer: 96回日本消化器病学会総会
  • Place of Presentation: 新潟
  • Year and Date: 2010-04-23
• [Presentation] Heat shock proteins derived from HBV-infected-hepatocyte enhance the function of regulatory T cells by TLR2 signaling (2010)
  • Author(s): Kondo Y, et al.
  • Organizer: APASL 2010
  • Place of Presentation: 北京
  • Year and Date: 2010-03-15
• [Presentation] HCV Replication in Human Lymphoid cells affects the development and proliferation activity (2009)
  • Author(s): Kondo Y, et al.
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] HCV replication in human lymphoid cells affects the development and proliferation activity (2009)
  • Author(s): 近藤泰輝, 等
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Possible pathogenecities of HCV replication in human lymphoid cells : Potential role in human autoimmune diseases (2009)
  • Author(s): 近藤泰輝, et al.
  • Organizer: AASLD Annual Meeting(アメリカ肝臓学会)
  • Place of Presentation: ボストン、アメリカ合衆国
  • Year and Date: 2009-11-02
• [Presentation] Stress-related proteins derived from HBV-infected-hepatocytes enhance the secretory functions of regulatory T cells (2009)
  • Author(s): Kondo Y, et al.
  • Organizer: AASLD
  • Place of Presentation: ボストン
  • Year and Date: 2009-11-01
• [Presentation] Possible pathogenecities of HCV eplication in human lymphoid cells : Potential role in human autoimmune diseases (2009)
  • Author(s): Kondo Y, Ueno Y, Machida K, et al.
  • Organizer: AASLD
  • Place of Presentation: ボストン
  • Year and Date: 2009-11-01
• [Presentation] 慢性B型肝炎における過剰な制御性T細胞活性化のメカニズム(ワークショップ3:免疫担当細胞異常からみた肝疾患の病態) (2009)
  • Author(s): 近藤泰輝、上野義之、下瀬川徹
  • Organizer: JDDW
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-14
• [Presentation] HBV感染肝細胞より産生されるsHSP60はTLR2を介してTregsの機能を増強する (2009)
  • Author(s): 近藤泰輝、上野義之、小林光樹、椎名正明、嘉数英二、井上淳、玉井恵一、二宮匡史、福島耕治、下瀬川徹
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04