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

Davidson, Fiona; Simmonds, Peter; Ferguson, Joy; Jarvis, L M; Dow, B. C.; Follett, E. A. C.; Seed, Clive R.; Krusius, Tom; Lin, Cheng-Ju; Medgyesi, G

doi:10.1099/0022-1317-76-5-1197

Cited by 391 publications

(297 citation statements)

References 37 publications

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“…IDU has been reported to account for 45% to 65% of HCV transmission, [17][18][19] but was more common (81%) among persons using a Veterans Administration hospital. 14 Blood transfusion has been identified as a risk exposure for 18% to 25% of persons. [17][18][19] The minimum prevalence estimate of anti-HCV among ANs is 0.8%, and 73.2% had HCV infections that were positive for HCV RNA.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and risk factors for hepatitis C in Alaska Natives

et al. 2004

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Large cohorts of persons infected with hepatitis C virus (HCV) that include patients with multiple risk exposures and behaviors have been rarely reported. We herein describe a population-based cohort of 759 Alaska Natives (AN) with HCV who were recruited into a long-term follow-up study. History of injection drug use (IDU) was reported by 60.1% and blood transfusion by 14.0%. The most common genotype was 1a (42.0%), followed by 1b (20.3%), 2b (14.7%), 3a (14.3%), and 2a (

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Section: Discussionmentioning

confidence: 99%

Epidemiology and risk factors for hepatitis C in Alaska Natives

et al. 2004

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“…16,17 HCV genotype was determined by restriction fragment length polymorphism based at the 5Ј-untranslated genomic region. 18,19 The nomenclature of HCV genotypes was according to the system proposed by Simmonds et al 20 Liver Histology. Hematoxylin-eosin-stained liver sections from all patients were evaluated by two blinded, independent investigators for their portal, periportal, and lobular activity, as well as fibrosis, according to the criteria proposed by Knodell et al 21 Summation of the three activity scores (portal ϩ periportal ϩ lobular) constituted the histological inflammatory activity index, and summation of all scores reflected total Knodell score.…”

Section: Methodsmentioning

confidence: 99%

Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C

et al. 1998

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Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) have been shown to play a role in host defense and pathogenesis of chronic HCV infection. Our aim was to test the hypothesis that intrahepatic HCV-specific CTL activity may impact subsequent response to interferon alfa (IFN-␣) therapy. Of the 37 patients that we have prospectively evaluated for HCV-specific CTL activity in liver, 21 received IFN therapy, and 19 completed a 6-month course and attended 6 to 18 months of follow-up. Intrahepatic CD8 ؉ cells were isolated from liver biopsy tissue and tested against target cells expressing HCV antigens to determine intrahepatic CTL activity. The relationship between treatment response and HCV-specific CTL activity and other factors known to associate with response (genotype, viremia, histology) was analyzed. HCV-specific CTL activity was detected in 9 of 21 patients (and 9 of 19 who completed therapy). After 6 months of IFN therapy, 8 of 19 (42%) patients had normal serum alanine transaminase (ALT) (complete responders). After 18 months of follow-up, only 3 patients (16%) had a sustained biochemical response. Of the 9 patients with detectable HCV-specific CTL activity in their liver before treatment, 7 (78%) developed a complete response. In contrast, only 1 of the 10 patients with no detectable HCV-specific CTL activity developed a complete response to IFN (P F .01). In 6 of 8 patients with a complete response, including the 3 sustained responders, the CTL response appeared to be directed predominately to the HCV core region. These data suggest that the host immune response, particularly that mediated by CD8 ؉ CTL, may be important in determining the outcome of IFN therapy for chronic HCV infection. Further understanding of the mechanism of action of IFN should impact the design of better therapeutic strategies against chronic HCV infection. (HEPATOLOGY 1998;28:225-230.)The host cellular immune defense, including the CD4 ϩ and CD8 ϩ T-cell response, is activated in patients with hepatitis C virus (HCV) infection. The intensity of the T-cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection. 1,2 In chronic viral infection, viral-specific CD8 ϩ cytotoxic T lymphocytes (CTL) have been shown to be important in host defense and in the control of the viral infection. [3][4][5][6][7] In lymphocytic choriomeningitis virus infection, virus-specific CTL activity reduces viral titers by 4 to 5 logs. 8 It is felt that CTL might lead to viral clearance through either direct lysis of infected cells or cytokine-mediated mechanisms. We and others have shown that HCV-specific CTL activity is detectable in the liver in a proportion of patients with chronic HCV infection. The presence of HCV-specific CTL activity in bulk-expanded CTL was found to be associated with a lower level of viremia and a greater inflammatory activity in the liver, suggesting that HCV-specific CTLs may assist in the control HCV infection, but, in so doing, contribute to hepatoce...

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“…HCV genotyping was performed by restriction fragment length polymorphism (RFLP) analysis of the 5Ј'NCR, basically as described. 25,27 Amplification of the NS3 Region and DNA Sequencing A segment of the NS3 region encompassing nucleotides 4429 to 4719 (positions referred to the HCV-1 prototype), which includes HLA-A2-restricted (KLVALGINAV) and HLA-A3-restricted (LIFCHSKKK) T-cell epitopes, was amplified by nested PCR. Several studies indicate that HCV Class I restricted T-cell epitopes located within the NS3 protein are commonly recognized by liver-infiltrating and circulating cytotoxic T lymphocytes (CTL) of HCV-infected patients.…”

Section: Hcv-rna Viral Load and Genotypingmentioning

confidence: 99%

Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis C

et al. 2004

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The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P ‫؍‬ .03), had a higher mean value of synonymous (dS) variations (P ‫؍‬ .02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients. (Liver Transpl 2004;10: 217-227.)

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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

Cited by 391 publications

References 37 publications

Epidemiology and risk factors for hepatitis C in Alaska Natives

Epidemiology and risk factors for hepatitis C in Alaska Natives

Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C

Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis C

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