1993 Fiscal Year Annual Research Report

B型肝炎ウイルス遺伝子変異による肝細胞障害・劇症化機序解明

Research Project

Project/Area Number	03454223
Research Institution	University of Tokyo
Principal Investigator	小俣政男東京大学, 医学部(病), 教授 (90125914)
Co-Investigator(Kenkyū-buntansha)	松村雅幸東京大学, 医学部(病), 医員多田稔東京大学, 医学部(病), 医員白鳥康史東京大学, 医学部(病), 助手 (70196624)
Keywords	HBウイルス / Core遺伝子 / 変異株 / 野生株 / HLA
Research Abstract	Precore遺伝子、Core遺伝子の塩基配列を決定したところ、B型肝炎のうち劇症肝炎、あるいは慢性肝炎で検索すると、病変を有する症例はすべてCore遺伝子の特定の部分に変異が認められた。さらに、ダックのB型肝炎ウイルス実験系を確立し、この変異を有するウイルスと野生株の混合感染を行うと、変異株は排除され、野生株が残存する傾向が認められた。このことから、B型肝炎ウイルスの増殖能は変異株は野生株に比べ極めて低いことが明かとなった。このことは、ヒト母子感染において野生株の伝播されるが変異株は排除され、B型肝炎ウイルスでは永年にわたりウイルスの原型が保たれることの機序と推察された。さらに、B型慢性肝炎の病態における宿主側の要因につき、HLA class Iの分離とそれに抱かれている蛋白(ウイルス蛋白の一部)の解析を開始した。現在、HLA class Iの分離をaffinity columnで行っている。この手法を用いて、B型慢性肝炎患者の肝内浸潤リンパ球を回収してHLA class Iの分離に進むところである。今後、回収したHLAをdigestionし、タンデム質量分折機にてアミノ酸分析を行い、それに見合うウイルス蛋白の同定を行う事としている。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Ehata T,Omata M et al: "Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis." J Clin Invest. 91. 1206-1213 (1993)
[Publications] Chuang WL,Omata M et al.: "Concentrating missense mutations in core gene of hepatitis B virus:evidence for adaptive mutation in chronic hepatitis B virus infection." Dig Dis Sci. 38. 594-600 (1993)
[Publications] Yokosuka O,Omata M et al.: "Expression of hepatitis C virus core protein as a fusion protein with maltose binding protein:detection of anti-hepatitis C core antibody by western blot." Dig Dis Sci. 38. 626-630 (1993)
[Publications] Kato N,Omata M et al.: "Quantification of hepatitis C virus by competitive reverse transcription-polymerase chain reaction:increase of the virus in advanced liver disease." Hepatology. 18. 16-20 (1993)
[Publications] Takano S,Omata M et al.: "Prospective asseament of donor blood screening for antibody to hepatitis C virus and high-titer antibody to hepatitis B core antigen as a means of preventing post transfuse hepatitis 〓" Hepatology. 18. 235-239 (1993)
[Publications] Kato N,Omata M et al.: "Detection of hepatitis C RNA in acute non-A,non-B hepatitis as an early diagnostic tool." Biochem Biophys Res Commun. 192. 800-807 (1993)
[Publications] Yokosuka O,Omata M et al.: "Anti-viral effect of recombinant interferon alfa-2a on hepatitis C virus." Int Hepatol Commun. 1. 128-132 (1993)
[Publications] Chien DY,Omata M et al.: "Use of recombinant HCV antigen in the serodiagnosis of hepatitis C virus infection:Significant improvement in HCV antibody detection as compared with the first generation HCV C10-3 ELISA and the synthetic peptide ETA tests." J Gastroenterology and Hepatology. 8. S33-S39 (1993)
[Publications] Chuang WL,Omata M et al.: "Precore mutations and core clustering mutations in chronic hepatitis B virus infection." Gastroenterology. 104. 263-271 (1993)
[Publications] Yokosuka O,Omata M et al.: "Expression of HCV E2/NS1 protein as a fusion protein with maltose binding protein:detection of anti-E2/NS1 antibody in chronic liver disease." Gut. 34. S64-S65 (1993)
[Publications] Takano S,Omata M et al.: "Prospective assessment of incidence of ful-minant hepatitis in post-transfusion hepatitis" Dig Dis Sci. 39. 28-32 (1994)

1993 Fiscal Year Annual Research Report

B型肝炎ウイルス遺伝子変異による肝細胞障害・劇症化機序解明

Principal Investigator

小俣 政男 東京大学, 医学部(病), 教授 (90125914)

Research Products

[Publications] Ehata T,Omata M et al: "Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis." J Clin Invest. 91. 1206-1213 (1993)

[Publications] Chuang WL,Omata M et al.: "Concentrating missense mutations in core gene of hepatitis B virus:evidence for adaptive mutation in chronic hepatitis B virus infection." Dig Dis Sci. 38. 594-600 (1993)

[Publications] Yokosuka O,Omata M et al.: "Expression of hepatitis C virus core protein as a fusion protein with maltose binding protein:detection of anti-hepatitis C core antibody by western blot." Dig Dis Sci. 38. 626-630 (1993)

[Publications] Kato N,Omata M et al.: "Quantification of hepatitis C virus by competitive reverse transcription-polymerase chain reaction:increase of the virus in advanced liver disease." Hepatology. 18. 16-20 (1993)

[Publications] Takano S,Omata M et al.: "Prospective asseament of donor blood screening for antibody to hepatitis C virus and high-titer antibody to hepatitis B core antigen as a means of preventing post transfuse hepatitis 〓" Hepatology. 18. 235-239 (1993)

[Publications] Kato N,Omata M et al.: "Detection of hepatitis C RNA in acute non-A,non-B hepatitis as an early diagnostic tool." Biochem Biophys Res Commun. 192. 800-807 (1993)

[Publications] Yokosuka O,Omata M et al.: "Anti-viral effect of recombinant interferon alfa-2a on hepatitis C virus." Int Hepatol Commun. 1. 128-132 (1993)

[Publications] Chuang WL,Omata M et al.: "Precore mutations and core clustering mutations in chronic hepatitis B virus infection." Gastroenterology. 104. 263-271 (1993)

[Publications] Yokosuka O,Omata M et al.: "Expression of HCV E2/NS1 protein as a fusion protein with maltose binding protein:detection of anti-E2/NS1 antibody in chronic liver disease." Gut. 34. S64-S65 (1993)

[Publications] Takano S,Omata M et al.: "Prospective assessment of incidence of ful-minant hepatitis in post-transfusion hepatitis" Dig Dis Sci. 39. 28-32 (1994)

小俣政男東京大学, 医学部(病), 教授 (90125914)