Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor

Chen, Chun‐Ming; You, Li Ru; Hwang, Lih Hwa; Lee, Yan-Hwa Wu

doi:10.1128/jvi.71.12.9417-9426.1997

Cited by 131 publications

(68 citation statements)

References 91 publications

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“…Finally, there are three recent papers reporting conflicting data on the possible interaction of HCV core protein with TNFa-induced apoptosis [27][28][29]. Similar to the findings reported here, Chen et al [27] did not detect a sensitization of stably transfected cell lines to TNFainduced cell death; on the other hand, both an enhancement [28] as well as an inhibition of TNFa-mediated apotosis [29] were reported. Once again, these diverging results might be due to different study designs, including different cell lines, expression constructs and the use of different HCV isolates.…”

Section: Discussionsupporting

confidence: 78%

Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells

Dumoulin

Bussche

Söhne

et al. 1999

Eur J Clin Investigation

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Section: Discussionsupporting

confidence: 78%

Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells

Dumoulin

Bussche

Söhne

et al. 1999

Eur J Clin Investigation

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“…Interestingly, HCV core protein has been shown to interact with several cellular factors including the tumor necrosis factor receptor-related lymphotoxin-␤ receptor (LT-␤R). 80,81 This interaction is capable of modulating one of the biological activities, i.e., cytolytic activity of LT-␤R triggering by its ligand LT-␣1␤2 in HeLa cells, 82,83 but not in HuH-7 cells. 80 HCV core has also been shown to interact with the tumor necrosis factor receptor 1 84 ; however, the effect of tumor necrosis factor-induced cytolytic activity is still controversial.…”

Section: Mechanisms Potentially Involved In Viral Persistencementioning

confidence: 99%

Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

1999

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The immune response to viral antigens is thought to be responsible for viral clearance and disease pathogenesis during hepatitis C virus (HCV) infection. In chronically infected patients, the T-cell response to the HCV is polyclonal and multispecific, although it is not as strong as the response in acutely infected patients who display a more vigorous T-cell response. Importantly, viral clearance in acutely infected patients is associated with a strong CD4 ؉ helper T-cell response. Thus, the dominant cause of viral persistence during HCV infection may be the development of a weak antiviral immune response to the viral antigens, with corresponding inability to eradicate infected cells. The most striking feature of hepatitis C is its tendency toward chronicity. The hepatitis C virus (HCV) contains a positive-stranded RNA genome of about 10 kilobases, which contains a single uninterrupted open reading frame that encodes a protein of 3010-3011 amino acids. 1,2 The virus is classified as a Flavivirus. HCV infects an estimated 400 million people, corresponding to more than 3% of the world population. 3 Numerous partial and complete nucleotide sequences have been derived from geographically widespread HCV isolates. The data indicate substantial sequence diversity within, and especially between, each geographic area. The European and American isolates appear to be more closely related to each other than to the Japanese isolates. Based on a polymerase chain reaction-based algorithm, a classification system has been proposed by Okamoto 4 and revised by Simmonds. 5 Different viral sequences (quasispecies) have been isolated from the same patient upon sequential sampling, and multiple isolates have been reported in a single sample. 6 The degree of similarity between isolates at the amino acid level varies from genome region to region. The nucleocapsid protein (core) has the highest sequence homology among all isolates sequenced to date. In contrast, the E1 and E2/NS1 regions present the highest degree of sequence variability among different isolates; in particular, the N terminal portion of E2/NS1 contains a hypervariable region of 30 amino acids, which shows extensive variation between virtually all known isolates. 7 The major extracellular loop of CD81, a cell-surface protein widely expressed on B and T lymphocytes and other cells including hepatocytes, has been shown to bind E2. 8 The recent success of isolating a cDNA clone capable of generating infectious RNA transcripts may be an important step toward the development of a tissue culture system. 9,10 The only animal model, the chimpanzee, mirrors several features of human HCV infection. Most importantly, the frequency of persistent infection is high in both species, and virus replication occurs despite evidence of cellular and humoral immune responses. 11,12 A key difference is that necroinflammatory lesions in chronically infected chimpanzees are almost always mild, whereas in humans, the disease spectrum is very wide, ranging from mild to severe hepatitis and end-sta...

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“…In addition to its structural property, HCV core protein has been demonstrated to regulate host cellular functions in cultured cells, e.g. gene transcription [5], signal transduction [6][7][8], and apoptosis [9,10,11]. Moreover, transgenic mice with HCV core protein developed liver steatosis and thereafter hepatocellular carcinoma [12,13].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the cleavage of signal peptide at the C-terminus of hepatitis C virus core protein by signal peptide peptidase

Hsieh

et al. 2007

J Biomed Sci

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Production of hepatitis C virus (HCV) core protein requires the cleavages of polyprotein by signal peptidase and signal peptide peptidase (SPP). Cleavage of signal peptide at the C-terminus of HCV core protein by SPP was characterized in this study. The spko mutant (mutate a.a. 189-193 from ASAYQ to PPFPF) is more efficient than the A/F mutant (mutate a.a 189 and 191 from A to F) in blocking the cleavage of signal peptide by signal peptidase. The cleavage efficiency of SPP is inversely proportional to the length of C-terminal extension of the signal peptide: the longer the extension, the less efficiency the cleavage is. Thus, reducing the length of C-terminal extension of signal peptide by signal peptidase cleavage could facilitate further cleavage by SPP. The recombinant core protein fused with signal peptide from the C-terminus of p7 protein, but not those from the C-termini of E1 and E2, could be cleaved by SPP. Therefore, the sequence of the signal peptide is important but not the sole determinant for its cleavage by SPP. Replacement of the HCV core protein E.R.-associated domain (a.a. 120-150) with the E.R.-associated domain (a.a.1-50) of SARS-CoV membrane protein results in the failure of cleavage of this recombinant protein by SPP, though this protein still is E.R.-associated. This result suggests that not only E.R.-association but also specific protein sequence is important for the HCV core protein signal peptide cleavage by SPP. Thus, our results suggest that both sequences of the signal peptide and the E.R.-associated domain are important for the signal peptide cleavage of HCV core protein by SPP.

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Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor

Cited by 131 publications

References 91 publications

Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells

Hepatitis C virus core protein does not inhibit apoptosis in human hepatoma cells

Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence

Characterization of the cleavage of signal peptide at the C-terminus of hepatitis C virus core protein by signal peptide peptidase

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