摘要:

Summary.The genomes of three new flavi‐like viruses, GBV‐A, GBV‐B and GBV‐C have been identified. Nucleic acid molecules corresponding to the genomes of GBV‐A and GBV‐B were isolated from tamarins with hepatitis which had been infected with the GB agent. RNA sequences corresponding to GBV‐C have been shown to be present in sera from humans with non‐A‐E hepatitis. Sequence comparisons show that these three viruses are more closely related to each other and to hepatitis C virus (HCV) than to any other known viruses. Together with HCV they appear to form a discrete cluster of related viruses within the larger genus of flaviviridae. The pathological significance of these viruses and their association with hepatitis is c

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00033.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Sequencing of the hepatitis C virus (HCV) has provided a better understanding of the natural history, immunology, and epidemiology of this virus. However, the morphology of HCV has not been definitively characterized. In this study, through a sequence of concentration processes, virus‐like particles were isolated from human serum and liver tissue, visualized by transmission electron microscopy and identified as hepatitis C virion by immunoelectron microscopy. Spherical flavi‐like virus particles, approximately 70 nm in diameter, were observed in the fraction with 1.04–1.12 g ml‐1sucrose density and bound to immunogold particles with monoclonal antibodies (mAb) against hepatitis C. The nucleocapsid of the particles, which were 50 nm in diameter, appeared to be icosahedral in structure and surrounded by an envelope covered with surface projections. A ‘tadpole’ form of particles was also observed. The findings indicate that the low buoyant density in sucrose and the morphological features of the hepatitis C virion are consistent with the characteristics of flaviviruses and p

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00034.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Hepatitis C virus (HCV) is a major health problem with a prevalence of 1% in the United States population, and a significant percentage of infected patients progress to chronic liver disease and cirrhosis. Interferon therapy has demonstrated that the immune system can be modulated to alter the acute course of the disease, but long‐term treatments remain elusive. Prevention of hepatitis C infection is therefore an important strategy to mitigate the impact of this disease. Initial attempts at vaccination have focused on recombinant envelope vaccines, which have shown an ability to protect against very low titre challenges of HCV in chimps. The need for vaccines capable of protecting against higher titre challenges has led to the search for alternative vaccine strategies. The most highly conserved structural protein in the HCV genome is the core protein, and vaccine strategies targeting the core protein have been proposed to increase vaccine efficacy. The variability of HCV core sequences and genotypes in the Ann Arbor patient population are not known, and the present study was undertaken to assess the theoretical feasibility of developing a HCV core vaccine by excluding promiscuous core (C) gene variability as a mechanism of vaccine failure. Results of nucleotide and deduced amino acid sequence analysis from 13 of 14 patients studied reveal a 93% nucleotide and 96.4% amino acid core sequence homology in the C gene regions studied. Genotype analysis revealed four of 14 to be type 1a and nine of 14 to be type 1b with one infection not being sufficiently characterized to determine genotype. These results demonstrate a sufficiently high degree of conservation of HCV core sequences in our patient population to permit design of a vaccine directed against core protei

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00035.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Recombinant interferon‐α2a (IFN‐α2a) in a total dose of 702 MU was given to 31 patients: nine with wild‐type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild‐type HBV and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild‐type HBV (A). Patients with low pre‐treatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild‐type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00036.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Precore mutants of hepatitis B virus (HBV) were looked for in 18 hepatitis B e antigen (HBeAg) carriers who were treated with recombinant interferon‐a (rIFN) and the results were compared with those obtained in 12 untreated carriers who underwent spontaneous HBeAb seroconversion. Molecular analysis of the HBV precore region was carried out by polymerase chain reaction (PCR) amplification and direct sequencing. Precore mutants with a stop codon at codon 28 were detectable at baseline in 19/30 carriers. However, wild‐type strains predominated in the baseline sera of both treated (n= 16) and untreated (n= 10) patients. Sera from the remaining four patients contained predominantly or exclusively mutant virions. Following IFN treatment, there was a shift from the wild‐type pattern to the mutant pattern in all patients, with the precore pattern prevailing in long‐term responders (six out of nine) compared with the non‐responders (none of nine). The wild‐type pattern predominated among the non‐responders (eightvsthree), suggesting that the long‐term response to IFN was associated with take‐over of precore mutants. There were no relationships between any pre‐treatment precore molecular pattern and disease severity or outcome of treatment. Precore mutants also took over in 10 of the 12 untreated patients (83%), who underwent spontaneous HBeAb seroconversion. Thus, a shift from wild‐type to precore mutant pattern occurs in most Italian patients undergoing IFN‐induced or spontaneo

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00037.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.A very high prevalence of anti‐hepatic C virus (anti‐HCV) antibodies (63/73, 86.3%) was noted among commercial plasma donors of an organization manufacturing blood products, studied in 1989. Retrospective serological analysis of these donors revealed continued high prevalence of anti‐HCV, i.e. 35/40 (87.5%) in 1988, 28/31 (90.3%) in 1987 and 86/94 (91.4%) in 1986. HCV RNA detection by polymerase chain reaction (PCR) demonstrated 15/33 (45.45%) plasma donors to be positive in 1989.Interestingly, 3/24 (12.5%) serum samples collected from employees of the organization were also anti‐HCV positive. All three anti‐HCV positive employees were directly associated with plasmapheresis. Of the three anti‐HCV positive employees one had been anti‐HCV positive since 1985, but the other two employees were negative during 1985–1987 and then became positive in 1987 and remained positive in 1989. One of these two employees was also a plasma donor.Commercial blood donors from a local blood bank had anti‐HCV prevalence of 13% which was significantly lower (P<0.001) when compared with plasma donors of the organization and significantly higher than volunteer blood donor

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00038.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large number of seropositive subjects have been detected and several reports have suggested a high prevelance of liver disease. The aim of this study was to evaluate the severity of liver disease in HCV‐positive blood donors in terms of the clinical, biochemical and histological abnormalities and to investigate the relationships between these features and the mode of transmission, duration of infection and viral genotype. We evaluated 54 consecutive blood donors who were positive for HCV both on serological testing and polymerase chain reaction. Twenty‐three (43%) had a history of intravenous drug abuse and 17 (31%) had received blood transfusions. In only two (4%) was no risk factor identified. The mean duration of infection in those with a clear history of HCV exposure was 12 years. Eighty‐three percent were HCV genotypes 1 or 3. All had abnormal liver biopsies with chronic hepatitis and several patients had periportal or portal‐portal fibrous septa, but there was none with architectural distortion or cirrhosis. There was no correlation between severity of liver disease and duration of HCV infection, mode of transmission or viral genotype.In the majority of HCV carriers detected at donor screening there is a chronic hepatitis with bridging necrosis in one third, but the degree of fibrosis is minimal and cirrhosis was not present in our patients. The long period of infection of many patients suggests that irreversible liver injury does not necessarily develop at an early stage despite persistent in

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00039.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY