http://repub.eur.nl/res/aut/468/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/17445/ 2008-09-24T00:00:00Z Hepatitis C virus (HCV), an enveloped positive stranded RNA virus, is the causative agent of non-A, non-B (NANB) hepatitis (27). The virus was identified and characterized by molecular cloning techniques using serum from a NANB hepatitis virus infected chimpanzee (15) and based on the similarity of the genome organization and hydropathy profiles of several precursor proteins classified as a member of the Flaviviridae family. However, the low sequence homology compared to other flaviviruses eventually lead to its classification into a new genus hepacivirus, distinct from the other flavivirus members (33, 74). Initial studies demonstrated that blood transfusions were the main transmission route that caused the HCV epidemic, especially prior to the period of HCV-contaminated blood screening in 1992 (50). HCV high-risk groups include recipients of multiple blood transfusion, hemophiliacs, hemodialysis patients and intravenous drug users. Modes of transmission include contact with contaminated-blood products, sharing needles, mother-to-child and sexual transmissions (69). Infection of the human liver is often clinically benign, with mild symptoms in the acute phase and fulminant hepatitis is very rare. The disease may even go unnoticed in cases of acute resolving HCV. In most cases (>70%) HCV infection leads to chronic persistent or active infection, often accompanied by complications of liver cirrhosis, or type II cryoglobulinaemia. The mechanisms of HCV persistence are not fully understood but the inability of the host innate and specific immune system to clear the virus is remarkable for a positive stranded RNA virus. HCV specific CD8+ T-cell responses are considered to play an important role in the containment and clearance of HCV infection but few of these cells are present in the liver and are unable to eradicate the infection. In addition, antibodies to HCV do not seem to play a major role in clearance of infection and re-infections are often observed with a different HCV strain, suggesting that immune responses to the initial strain did not protect against an infection with another strain of HCV (43). http://repub.eur.nl/res/pub/28942/ 2008-05-01T00:00:00Z Hepatitis C virus (HCV) genomes exhibit high nucleotide sequence diversity. In this study, we performed complete genome sequence analysis of 11 HCV genotype 6 samples from Vietnam and Thailand. We identified nine HCV complete genomes belonging to subtypes 6a (D9), 6e (D42 and D88), 6f (TH52), 6i (TH24), 6l (D33), 6n (TH22 and TH31) and 6o (D85). Phylogenetic analysis of the core/E1 and NS5B regions from unclassified genotype 6 isolates from Asian immigrants in Canada revealed that two other viruses (D49 and D83) could be classified as novel candidates of HCV subtypes 6t and 6u. http://repub.eur.nl/res/pub/35110/ 2007-11-01T00:00:00Z Hepatitis C virus (HCV) has a linear positive-stranded RNA genome of ∼9,600 nucleotides in length and displays a high level of sequence diversity caused by high mutation rates and recombination. However, when we performed long distance reverse transcription-PCRs on HCV RNA isolated from serum of chronic HCV patients, not only full-length HCV genomes but also HCV RNAs which varied in size from 7,600 to 8,346 nucleotides and contained large in-frame deletions between El and NS2 were amplified. Carefully designed control experiments indicated that these deletion mutants are a bona fide natural RNA species, most likely packaged in virions. Moreover, deletion mutants were detected in sera of patients infected with different HCV genotypes. We observed that 7/37 (18.9%) of genotype 1, 5/43 (11.6%) of genotype 3, and 4/13 (30.7%) of genotype 6 samples contained HCV deletion mutant genomes. These observations further exemplify HCVs huge genetic diversity and warrant studies to explore their biological relevance. Copyright http://repub.eur.nl/res/pub/8468/ 2003-01-01T00:00:00Z Although transmission of human hepatitis B virus (HBV) variants to nonhuman primates is well documented, it remains to be elucidated whether nonhuman primate HBV is transmissible to humans. The prevalence and transmission routes of gibbon HBV were analysed in 101 captive gibbons in Thailand. Approximately 40 % of these animals showed at least one marker of HBV infection; 19 animals were chronic HBV carriers, characterized by elevated levels of alanine amino transferase and the presence of HBV DNA. Some of the chronic animals were found to be anti-HBc (HBV core antigen) negative (4 of 19), while precore promoter point mutations (nt 1762 or 1764) were determined in four animals by RFLP analysis. Phylogenetic tree analysis of the complete surface gene sequences revealed that gibbon viruses clustered separately from hepadnaviruses of other hosts. Evidence for horizontal and vertical transmission in captive gibbons was obtained. HBV DNA was also detected in the saliva of HBV carrier gibbons. Although some of the animal caretakers at the Krabok Koo Wildlife Breeding Centre were found to be chronic HBV carriers, genotype and sequence analysis did not reveal any evidence for zoonotic disease transmission.