東北大学 · 医学
本研究室は、ウイルス性肝炎の病原メカニズムと治療戦略の解明を柱としており、特にヘパチティスEウイルス(HEV)とヘパチティスBウイルス(HBV)のゲノム・病原性・ウイルス成熟メカニズムに焦点を当てた研究を進めています。HEVの遺伝子多様性と重症度の関連、HBVの細胞内成熟・放出機構におけるMVBおよびオートファジー系の役割、さらには天然由来化合物のウイルス抑制作用についても解明を進めています。
Figures are computed from collected data and may differ slightly.
It was suggested that hepatitis E virus (HEV) genotype 4 is associated more closely with the severity of hepatitis E than genotype 3, although the virological basis remains unknown. The aim of this study was to examine whether genomic differences among genotype 4 HEVs are responsible for the development of fulminant hepatitis. Full-length sequences of genotype 4 HEVs from three patients with fulminant hepatitis and six patients with acute self-limited hepatitis were determined. The sequences wer
The cellular mechanisms by which hepatitis B virus (HBV) is assembled and exported are largely undefined. Recently, it has been suggested that these steps require the multivesicular body (MVB) and the autophagic machinery. However, the mechanisms by which HBV might regulate these compartments are unclear. In this study, we have found that by activating Rab7a, HBV alters its own secretion by inducing dramatic changes in the morphology of MVB and autophagic compartments. These changes are characte
A previous study revealed a high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis delta virus (HDV) RNA among 249 apparently healthy individuals (mean+/-standard deviation age, 48.4+/-13.9 years; 126 males and 123 females) in Ulaanbaatar, Mongolia. To investigate further the prevalence of HDV infection there, the same serum samples obtained from the cohort were tested for the presence of immunoglobulin G (IgG) class antibody to HDV (anti-HDV) by a newly developed enzyme-linked imm
Hepatitis B virus (HBV) infection is a worldwide health problem because of its potential to cause liver cirrhosis and hepatocellular carcinoma. Silibinin is a constituent of an extract of milk thistle, which is empirically used as a herbal medicine for the protection of liver, but its detailed effects on HBV are unknown. Because a previous study reported that silibinin hinders clathlin-mediated endocytosis (CME), we aimed to test whether silibinin inhibits the entry of HBV into hepatocytes. Usin
To investigate the efficacy of long-term lamivudine (3TC) and adefovir dipivoxil (ADV) combination therapy in 3TC-resistant chronic hepatitis B virus (HBV) infected patients, we analysed 28 3TC-resistant patients treated with the combination therapy during 47 months (range, 9-75). At 12, 24, 36, and 48 months, the rates of virological response with undetectable HBV DNA (≤ 2.6 log copies/mL) were 56, 80, 86, and 92%, respectively. Among 17 hepatitis B e antigen (HBeAg)-positive patients, HBeAg di
Full-length sequences were determined for a human hepatitis E virus (HEV) isolate (HE-JA04-1911) and two swine HEV isolates (swJ8-5 and swJ12-4) that belong to one of three clusters within genotype 3 in Japan and are close to Spanish isolates according to their partial sequences. The three HEV isolates were 89.7-92.9 % identical to each other, but only 80.7-83.0 % similar to 21 HEV strains of the same genotype isolated in Canada, Kyrgyzstan, the USA and Japan over their entire genome. On compari
The frameshift insertion/deletion in the precore region enhanced HBV replication and might be associated with the development of FH by the subgenotype B1/Bj HBV.
Currently, the hepatocellular trafficking pathways that are used by the hepatitis B virus (HBV) during viral infection and shedding are poorly defined. It is known that the HBV uses late endosomal and multivesicular body (MVB) compartments for assembly and release. The intraluminal vesicles (ILVs) generated within MVBs have also been implicated in the late synthesis stages of a variety of pathogenic viruses. We recently observed that the HBV within infected hepatocytes appears to associate with
The envelope of hepatitis B virus (HBV), which is required for the entry to hepatocytes, consists of a lipid bilayer derived from hepatocyte and HBV envelope proteins, large/middle/small hepatitis B surface antigen (L/M/SHBs). The mechanisms and host factors for the envelope formation in the hepatocytes are being revealed. HBV-infected hepatocytes release a large amount of subviral particles (SVPs) containing L/M/SHBs that facilitate escape from the immune system. Recently, novel drugs inhibitin
Hepatitis E virus (HEV) is one of the causative agents of acute or fulminant hepatitis. Viral factors may play a role in the pathogenesis of fulminant hepatitis E. We aimed to investigate the nucleotide substitutions of the HEV genome affecting the severity of hepatitis E. The comparison of 28 reported full-length nucleotide sequences of genotype 4 HEV showed that the substitution of C at nucleotide 5907 (C5907) was most closely associated with fulminant hepatitis (fulminant hepatitis, 100%; acu
Viruses are considered to use vesicular trafficking in infected cells, but the details of assembly/release pathways of hepatitis B virus (HBV) are still unknown. To identify key regulators of HBV production, we performed short interfering RNA (siRNA) screening for Rab proteins, which are considered to act as molecular switches in vesicular trafficking using HepG2.2.15 cells. Among 62 Rab proteins, the suppression of Rab5B most significantly increased HBV DNA in the culture supernatant. Surprisin
Although a lower rate of HCC occurrence in HBV/B was shown by an age/sex-matched analysis than that in HBV/C, patients with HBV/B were significantly older and had a comparative risk of HCC occurrence in nucleos(t)ide analog-treated patients.
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