At least 12 genotypes of hepatitis C virus predicted by sequence analysis of the putative E1 gene of isolates collected worldwide.

Bukh, Jens; Purcell, Robert H.; Miller, R.H.

doi:10.1073/pnas.90.17.8234

Cited by 385 publications

(312 citation statements)

References 28 publications

(14 reference statements)

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“…Mammalian expression vectors containing the core (aa 1 to 191) and the E1E2p7 (aa 155 to 809) regions of the HCV genome obtained by RT-PCR from HCV-positive human serum were cloned into the pRc/CMV mammalian expression vector. The nucleotide sequence of the clones was determined and classified the HCV isolate as type 1a (9). In the E1E2p7 construct, the signal sequence of E1 protein (aa 155 to 191) was included to allow proteins to be transported into the endoplasmic reticulum membrane.…”

Section: Methodsmentioning

confidence: 99%

Repression of Interferon Regulatory Factor 1 by Hepatitis C Virus Core Protein Results in Inhibition of Antiviral and Immunomodulatory Genes

Ciccaglione

Stellacci

Marcantonio

et al. 2007

J Virol

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Hepatitis C virus (HCV) proteins are known to interfere at several levels with both innate and adaptive responses of the host. A key target in these effects is the interferon (IFN) signaling pathway. While the effects of nonstructural proteins are well established, the role of structural proteins remains controversial. We investigated the effect of HCV structural proteins on the expression of interferon regulatory factor 1 (IRF-1), a secondary transcription factor of the IFN system responsible for inducing several key antiviral and immunomodulatory genes. We found substantial inhibition of IRF-1 expression in cells expressing the entire HCV replicon. Suppression of IRF-1 synthesis was mainly mediated by the core structural protein and occurred at the transcriptional level. The core protein in turn exerted a transcriptional repression of several interferonstimulated genes, targets of IRF-1, including interleukin-15 (IL-15), IL-12, and low-molecular-mass polypeptide 2. These data recapitulate in a unifying mechanism, i.e., repression of IRF-1 expression, many previously described pathogenetic effects of HCV core protein and suggest that HCV core-induced IRF-1 repression may play a pivotal role in establishing persistent infection by dampening an effective immune response.Infection with hepatitis C virus (HCV) represents the major cause of liver disease, affecting more than 170 million individuals worldwide (26). After a subclinical phase, more than 80% of patients progress to persistent HCV infection, which is the leading cause of chronic liver disease associated with cirrhosis and hepatocellular carcinoma (13). The persistence of the virus in the majority of infected individuals is linked to the ability of HCV to evade and/or antagonize the host immune response at both the local and systemic levels. Accordingly, although hepatocytes are a major target of HCV infection, the virus can also replicate in immune cells, including effector cells (1,11). In this respect, resistance to interferon (IFN) therapy is a hallmark of evolution in persistence, indicating that knocking down the antiviral and immunomodulating effects of IFN is a successful strategy for evading the host immune surveillance (21). The production and secretion of IFN type I is pivotal in inducing a global antiviral state through paracrine IFN production and the subsequent activation of interferon-stimulated genes (ISGs) within the infected cells and in the surrounding tissues (70). The role of IFN in HCV infection is thus crucial (21). Functional genomic analyses from cohorts of human subjects with chronic infection have shown that infection is associated with a gene expression profile marked by ISGs whose level of expression is related to different degrees of liver fibrosis and cirrhosis (67). Similarly, gene expression profiling has demonstrated that acute resolving infections in chimpanzees are associated with high levels of hepatic ISG expression (4).The single-stranded RNA genome of HCV is translated into a polypeptide precursor of 3,010 amino aci...

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Section: Methodsmentioning

confidence: 99%

Repression of Interferon Regulatory Factor 1 by Hepatitis C Virus Core Protein Results in Inhibition of Antiviral and Immunomodulatory Genes

Ciccaglione

Stellacci

Marcantonio

et al. 2007

J Virol

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“…The presence of a G at position -99 produces a sequence in RT-PCR products that is recognized by the restriction enzymes BstUI and MvnI. There are no other polymorphisms that affect this restriction site amongst the type 1 viruses surveyed, except for a single type la virus (DK9) that has a C to U substitution at position -100 (Bukh et al, 1992(Bukh et al, , 1993 and in any case lacks the G at position -99. Accordingly, the subtype of type 1 viruses can usefully be predicted on the basis of the RFLP pattern would appear as type la in this assay.…”

Section: Predicted Electropherotypes Of Published Hc V 5"ncr Sequencementioning

confidence: 99%

“…Previous work has demonstrated that all six currently defined major genotypes of HCV (Simmonds et al, 1993a;Bukh et al, 1993) can be distinguished on the basis of RFLP analysis of RT-PCR products derived from the 5'NCR (Nakao et al, 1991;McOmish et al, 1993McOmish et al, , 1994Simmonds et al, 1994b). In one previous study, amplified DNA is cleaved with HaeIII-RsaI in one reaction and with MvaI-HinfI in a second, and the virus genotype is deduced by the combination of electropherotypes produced .…”

Section: Predicted Electropherotypes Of Published Hc V 5"ncr Sequencementioning

confidence: 99%

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Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5' non-coding region

Davidson

Simmonds²,

Ferguson³

et al. 1995

Journal of General Virology

391

285

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A method is described for identifying different genotypes of hepatitis C virus (HCV) by restriction endonuclease cleavage of sequences amplified by PCR from the 5' non-coding region. Using the enzymes HaeIII-RsaI and HinfI-MvaI, followed by cleavage with BstU1 or ScrFI, it was possible to identify and distinguish HCV genotypes la, lb, 2a, 2b, 3a, 3b, 4, 5 and 6. The method was used to investigate the prevalence of these genotypes in 723 blood donors in 15 countries, the largest survey to date, and one which covered a wide range of geographical regions (Europe, America, Africa and Asia). These results, combined with a review of the existing literature, indicate the existence of several distinct regional patterns of HCV genotype distribution, and provide the framework for future detailed epidemiological investigations of HCV transmission.

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“…Nucleotide sequence differences of both the coding and non-coding region detected in the virus isolates have led to a classification of HCV into several genotypes [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to hepatitis C virus genotypes in chronic hepatitis C

Pham

Martinot‐Peignoux

Mosnier

et al. 1995

Clinical and Experimental Immunology

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SUMMARYThe pathogenic mechanisms that lead to chronic hepatitis C are unknown. As hepatitis C virus (HCV) has been shown to induce T cell response, we assessed whether a partictilar T lymphocyte subset could be preferentially detected in theliver of patients with chronic hepatitis C in relation to viraemia or HCV genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26 patients by flow cytometry and immunohistochemistry. Viraemia was quantified by branched DNA assay. Using this assay, HCV RNA was not detectable in six patients. HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 x 10''Eq/ml. Genotyping was performed using a line probe assay. Type la. lb. 2a, 3a and 4a were found to infect 2. 10. 2, 7 and 3 patients, respectively. The CD4 ^ /CD8 * ratio of liver-derived lymphocytes was significantly higher [P < 001) in patients with detectable viraemia than in patients without detectable viraemia. In contrast, neither the percentage of ^/i^ T lymphocytes nor that of CD2^CD57^ cells was different in the groups. When comparing the CD4^/CD8^ ratio, the percentage of-y/^ T lymphocytes or CD2^CD57' cells according to genotype, the differences were not significant. These results suggest that the CD4^/ CD8"^ratio of liver-derived lymphocytes is related to viraemia but not to HCV genotypes in patients with chronic hepatitis C. and that T lymphocytes may be involved in the pathogenesis of liver le.sions in chronic hepatitis C, Keywords hepatitis C virus chronic hepatitis C liver-derived lymphocytes lymphocyte subsets viraemia hepatitis C virus genotype

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At least 12 genotypes of hepatitis C virus predicted by sequence analysis of the putative E1 gene of isolates collected worldwide.

Abstract: In a previous study we sequenced the 5' non-

Cited by 385 publications

References 28 publications

Repression of Interferon Regulatory Factor 1 by Hepatitis C Virus Core Protein Results in Inhibition of Antiviral and Immunomodulatory Genes

Repression of Interferon Regulatory Factor 1 by Hepatitis C Virus Core Protein Results in Inhibition of Antiviral and Immunomodulatory Genes

Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5' non-coding region

CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia and not to hepatitis C virus genotypes in chronic hepatitis C

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