Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic steatosis has been reported as one of the characteristics which discriminates hepatitis C from other forms of hepatitis, besides lymphoid follicles and bile duct damage. However, it is unclear whether or not the presence of hepatitis C virus (HCV) itself is associated with the development of steatosis. The possibility that the HCV itself is directly related to the development of steatosis was examined. The intrahepatic core protein levels, as a marker of the HCV load, were correlated with the presence of steatosis in 43 patients with chronic hepatitis C. Among 43 patients studied by Western blotting, the core protein was detected in the liver in 27 (62.8%). On the other hand, hepatic steatosis was observed in 21 (48.8%) of the 43 patients. Importantly, the core protein was detectable in 19 (90.4%) of the 21 patients with steatosis, while it was detected in only 8 (36.4%) of the 22 patients without steatosis (P = 0.008). However, serum HCV-RNA levels as determined by the Amplicor monitor were not significantly different between patients with and without steatosis. Multivariate analysis showed that the serum alanine aminotransferase level (P = 0. 013), body mass index (P = 0.038), and intrahepatic HCV core protein positivity (P = 0.038) were the independent parameters best predictive of steatosis. These results indicate a close relationship between intrahepatic HCV and the development of steatosis, and suggest a possible role of the HCV itself or core protein in the pathogenesis of steatosis in human chronic hepatitis C.
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PMID:Steatosis and intrahepatic hepatitis C virus in chronic hepatitis. 1045 47

Hepatitis C virus (HCV) is the major etiological agent of blood-borne non-A non-B hepatitis and a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV core protein is a multifunctional protein with regulatory functions in cellular transcription and virus-induced transformation and pathogenesis. Here we report on the identification of a bZIP nuclear transcription protein as an HCV core cofactor for transformation. This bZIP factor, designated LZIP, activates CRE-dependent transcription and regulates cell proliferation. Loss of LZIP function in NIH 3T3 cells triggers morphological transformation and anchorage-independent growth. We show that HCV core protein aberrantly sequesters LZIP in the cytoplasm, inactivates LZIP function and potentiates cellular transformation. Our findings suggest that LZIP might serve a novel cellular tumor suppressor function that is targeted by the HCV core.
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PMID:Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation. 1067 42

Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite successful resection, the remnant cirrhotic liver frequently develops new HCC lesions, seriously curtailing long-term survival. All-out efforts should be directed to the prevention of HCC, through prevention of viral hepatitis, prevention of acute hepatitis from becoming chronic, prevention of chronic hepatitis from progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC (chemoprevention). At the moment, very few such studies exist.
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PMID:Hepatocellular carcinoma. 1072 7

Hepatitis virus, especially hepatitis C virus(HCV), is suggested to be associated with lymphomagenesis. A high prevalence(33%) of HCV among non-Hodgkin's lymphoma(NHL) patients has been reported mainly in Italy, but the prevalence is low in other countries. HCV-related NHL is varied histopathologically, including diffuse large B cell lymphoma, immunocytoma or follicular lymphoma(REAL). The HCV genotypes involved are 1b, 2a or 2c(Simmonds). Although HCV RNA + strand has been detected in lymphoma tissue in various studies, there are not many studies in which HCV RNA-strand has been detected. Recent studies have shown that BCL-2 plays an important role in lymphoproliferation by suppressing apoptosis, that HCV core protein regulates c-myc transcription and that BCL-2 and c-myc work together in lymphomagenesis. It seems difficult to provide reasonable explanations regarding these puzzling epidemiological findings and lymphomagenesis.
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PMID:[Hepatitis virus and malignant lymphoma]. 1074 Nov 25

GB virus type C (GBV-C) is a member of the hepacivirus genus within the Flaviviradae. Persistent GBV-C infection is common in humans, yet it remains unclear if GBV-C causes any disease. Although GBV-C infection has been associated with acute non-A to non-E post-transfusion hepatitis, it does not appear to cause chronic hepatitis. GBV-C is closely related to hepatitis C virus (HCV), but indirect evidence suggests that it does not encode a core protein at the amino terminus of the open reading frame (ORF). This has led to speculation that GBV-C does not have a nucleocapsid. We evaluated the buoyant density of GBV-C, and found very low density particles consistent with virions, and intermediate density particles consistent with nucleocapsids in GBV-C-infected people. In addition, electron microscopy demonstrated an apparent nucleocapsid within an enveloped particle. Although these biophysical data strongly suggest that GBV-C utilizes a nucleocapsid, they do not indicate the origin of the protein content of this particle. To assess this, we evaluated patient plasma for reactivity with a synthetic oligopeptide representing a conserved region near the amino terminus of the predicted ORF. Specific antibody was detected in some individuals, similar to data of Feucht et al. who identified antibody against a recombinant core protein in GBV-C-infected people. These data indicate that GBV-C particles contain nucleocapsids. At least in some patients, the region upstream of the GBV-C E1 protein coding region appears to be expressed, and this region may represent the structural protein of the nucleocapsid.
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PMID:Visualization and characterization of GB virus-C particles: evidence for a nucleocapsid. 1076 30

The humoral immune response to acute infection by hepatitis C virus (HCV) is not yet perfectly clear in terms of immunoglobulin (Ig) response, diversity of HCV antigen, and the relation with hepatitis severity and antibody response. Serum IgM and IgG anti-HCV levels in patients with HCV and either acute hepatitis (AH) or fulminant hepatitis (FH) were investigated; the diversity of HCV antigen was investigated by RIBA test III. Of 22 AH patients, 12 (54.5%) were positive for IgM anti-HCV, mainly reacting to HCV core protein. The mean interval until the appearance of IgM anti-HCV after onset was 24.1+/-26.2 days. IgG anti-HCV mainly reacted to both core and NS-3 antigen, appearing 42.6+/-42.1 days after onset. From a serial study of 15 AH patients, it was considered that in seven AH patients (46. 7%), the IgM response would precede the IgG response. In another two AH patients, IgM anti-HCV was not detected during the acute disease phase. Of 48 chronic hepatitis patients with HCV-RNA, 40 patients were positive for IgM anti-HCV. Therefore, IgM anti-HCV was useful for diagnosis in some of the AH patients, but it was difficult to use for distinguishing between acute and chronic infection. All four FH patients with HCV-RNA were positive for both IgM and IgG antibody to HCV at onset. Their antibody titres were higher than those of AH patients. These results suggested that, as in FH due to HBV, FH due to HCV could induce strong and rapid humoral immunity.
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PMID:Humoral immune response in Japanese acute hepatitis patients with hepatitis C virus infection. 1097 46

A line of hepatitis C virus (HCV) transgenic mice was established previously that was mediated by Cre/loxP system using HCV cDNA, including core, E1, E2 and NS2 genes. Intravenous infection of a recombinant adenovirus that expresses Cre DNA recombinase (AxCANCre) induced HCV structural protein expression in the liver of transgenic mice. HCV core protein production and transgene recombination in the mouse liver were serially evaluated after AxCANCre infusion. Core proteins were expressed efficiently and transgene was almost completely recombined in the liver of mice after 3 days and then the levels of both core protein production and transgene recombination decreased continuously for 28 days. However, 30.6% of the transgene recombination remained at 28 days and only 2.7% of core production remained at 28 days after infection. Compared with nontransgenic controls, the serum alanine aminotransferase levels in transgenic mice were significantly higher 10, 14, and 21 days after adenovirus infection. Histological scoring also indicated severe pathological changes in the liver of transgenic mice after adenovirus infection. AxCANCre infusion increased CD8+ lymphocyte infiltration into the liver of transgenic mice compared with that of non-transgenic controls. Furthermore, cytotoxic T lymphocytes (CTLs) isolated from transgenic mice during liver injury were specific for the HCV proteins. These results suggest that HCV structural proteins expressed in the liver of transgenic mice enhanced liver injury. HCV-specific CTLs may be to enhance hepatitis. Thus, the present HCV transgenic mouse model provides a useful model of liver injury due to HCV, and the host immune response may play a pivotal role(s) in the pathogenesis of HCV.
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PMID:Possible role of cytotoxic T cells in acute liver injury in hepatitis C virus cDNA transgenic mice mediated by Cre/loxP system. 1105 40

Hepatitis B virus (HBV), a small DNA containing virus that replicates via reverse transcription, causes acute and chronic B-type hepatitis in humans. The limited success of current therapies for chronic infection has prompted exploration of alternative strategies. Capsid-targeted viral inactivation is a conceptually powerful approach that exploits virion structural proteins to target a degradative enzyme specifically into viral particles. Its principal feasibility has been demonstrated in retroviral model systems but not yet for a medically relevant virus outside the retrovirus family. Recently, we found that C proximal fusion to the HBV capsid protein of the Ca(2+)-dependent nuclease (SN) from Staphylococcus aureus yields a chimeric protein, coreSN, that in Escherichia coli coassembles with the wild-type capsid protein into particles with internal SN domains. Here we show that, in HBV co-transfected human hepatoma cells, less than 1 coreSN protein per 10 wild-type core protein subunits reduced titers of enveloped DNA containing virions by more than 95%. The antiviral effect depends on both an enzymatically active SN and on the core domain. CoreSN does not block assembly of RNA containing nucleocapsids but interferes with proper synthesis of viral DNA inside the capsid, or leads to rapid DNA degradation. Our data suggest an intracellular nuclease activation that, owing to the characteristics of HBV morphogenesis, is nonetheless highly virus specific. HBV may therefore be particularly vulnerable to the capsid-targeted viral inactivation approach.
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PMID:Significant interference with hepatitis B virus replication by a core-nuclease fusion protein. 1112 40

Overwhelming lines of epidemiological evidence have indicated that chronic infection with hepatitis C virus(HCV) poses a major risk toward development of hepatocellular carcinoma(HCC). In the pathogenesis of HCC associated with HCV, it remains controversial whether these hepatitis viruses play a direct role or merely serve for an indirect role. By virtue of transgenic mouse established by us, it has become evident hat the core protein of HCV has an oncogenic potential. The findings in our studies indicate that HCV is directly involved in hepatocarcinogenesis, albeit other factors such as continued cell death and regeneration associated with chronic hepatitis may play a role, as well. Combined, our results suggest that there would be a mechanism for the development of HCC in persistent infection with hepatitis C virus that is distinct from those for the other cancers. Similar to the pathogenesis of other malignancies represented by colorectal cancer, the accumulation of a set of genetic aberrations may also be necessary for a multi-stage development of HCC. However, HCV core protein, to which an oncogenic potential is ascribed, may allow some of the multiple stages skipped in hepatocarcinogenesis. Unlike for the other cancers, therefore, infection with HCV may be capable of eliciting HCC in the absence of a complete set of genetic aberrations. Such a scenario would explain unusually high incidence and multicentric nature of HCC developing in chronic hepatitis C.
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PMID:[HCV core gene transgenic mouse as a model for viral hepatocarcinogenesis]. 1149 35

Injection of particulate hepatitis B virus surface antigen (HBsAg) in mice leads to the induction of a HBsAg-specific class-I-restricted cytotoxic T lymphocyte (CTL) response. It is proposed that any protein internal to HBsAg will also be able to elicit a specific CTL response. In this study, several carboxy-terminal truncations of hepatitis C virus (HCV) core protein were fused to varying lengths of amino-terminal truncated large hepatitis delta antigen (L-HDAg). These constructs were analysed for their ability to be expressed and the particles secreted in the presence of HBsAg after transfection into HuH-7 cells. The secretion efficiency of the various HCV core-HDAg chimeric proteins was generally poor. Constructs containing full length HDAg appeared to be more stable than truncated versions and the length of the inserted protein was restricted to around 40 amino acids. Thus, the use of L-HDAg as a chimera to package foreign proteins is limited. Consequently, a polyepitope (polytope) containing a B-cell epitope from human papillomavirus (HPV 16) and multiple T-cell epitopes from the HCV polyprotein was used to create the construct, L-HDAg-polyB. This chimeric protein was shown to be reliant on the co-expression of HBsAg for secretion into the cell culture fluid and was secreted more efficiently than the previous HCV core-HDAg constructs. These L-HDAg-polyB virus-like particles (VLPs) had a buoyant density of approximately 1.2 g/cm3 in caesium chloride and approximately 1.15 g/cm3 in sucrose. The VLPs were also immunoprecipitated using an anti-HBs but not an anti-HD antibody. Thus, these recombinant VLPs have similar biophysical properties to L-HDAg VLPs.
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PMID:Development and characterisation of recombinant hepatitis delta virus-like particles. 1155 8


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