Primates in the study of hepatitis viruses

There is no a conventional tissue culture system for the propagation of the hepatitis viruses and only some of them can be maintain in continuous cell culture in particular conditions. A transmissibility of hepatitis is limited to primates. The narrow host specificity may help to establish the classification of the hepatitis viruses and their mode of transmission. Moreover, the primate animal model provided the most accessible source of viruses and for clinical reasons presents the only opportunity for the studies of pathogenic mechanisms involving cellular immunity with allogenic restriction. The marmosets and chimpanzees susceptible to the hepatitis A and B viruses, respectively are the primates of choice for the experimental models. For the studies on parenterally transmitted NANB hepatitis the chimpanzee and some rhesus monkeys may provide an animal system. At last, most of the primates seem to be susceptible to agent responsible for the water-borne non A non B hepatitis.     

An overview of hepatitis B serology screening check-up program among Thai workers

In Thailand, hepatitis B virus (HBV) infection is hyperendemic; approximately 5 million Thais are chronic HBV carriers. Here, an overview of hepatitis B serology among Thai workers who got the screening check-up program of King Chulalongkorn Memorial Hospital during January 1998 to December 2000 is reported. The data from hepatitis B serology examinations of 650 Thai workers who visited the Out-Patient Division, King Chulalongkorn Memorial Hospital during the study period for the screening program before starting work was analyzed. Among the subjects examined, 107 were HBsAg-, anti-HBc-; 64 were HBsAg+, anti-HBc+; and 479 were HBsAg-, anti-HBc+. Not unexpectedly, in the present study, the rate of chronic hepatitis B infection among the subjects is high (9.8%). Screening for parasitic infection among this population can help decrease the development of late complications as well as rejection of laborers by their employers.     

Resistance mechanisms to plant viruses: an overview

To obtain virus-resistant host plants, a range of operational strategies can be followed nowadays. While for decades plant breeders have been able to introduce natural resistance genes in susceptible genotypes without knowing precisely what these resistance traits were, currently a growing number of (mostly) dominant resistance genes have been cloned and analyzed. This has led not only to a better understanding of the plant's natural defence systems, but also opened the way to use these genes beyond species borders. Besides using natural resistance traits, also several novel, "engineered" forms of virus resistance have been developed over the past 15 years. The first successes were obtained embarking from the principle of pathogen-derived resistance (PDR) by transforming host plants with viral genes or sequences with the purpose to block a specific step during virus multiplication in the plant. As an unforeseen spin-off of these investments, the phenomenon of post-translational gene silencing (PTGS) was discovered, which to date is by far the most successful way to engineer resistance. It is generally believed that PTGS reflects a natural defence system of the plant, and part of the hypothesized components required for PTGS have been identified. As counteracting strategy, and confirming PTGS to be a natural phenomenon, a considerable number of viruses have acquired gene functions by which they can suppress PTGS. In addition to PDR and PTGS, further strategies for engineered virus resistance have been explored, including the use of pokeweed antiviral protein (PAP), 2',5'-oligoadenylate synthetase and "plantibodies". This paper will give a brief overview of the major strategies that have become operational during the past 10 years.     

A second group of hepatitis C viruses

cDNA clone 11–7 was isolated by immunoscreening a cDNA library that was prepared from a pooled plasma of non-A non-B hepatitis (NANBH) patients using expression vector gt 11. This cDNA corresponds to known nucleotide positions 3983–4745 of the genome of hepatitis C virus (HCV). This clone was used as a probe for screening the HCV-related cDNAs in a cDNA library similarly prepared by using gt 10. As a result, six more cDNA clones were isolated and analyzed for their nucleotide sequences. The results strongly suggested that there are at least two groups of HCV, group I and group II. According to our classification, the prototype HCV and clone 11–7 belong to group I HCV, and their nucleotide and deduced amino acid sequences were diverged from those of group II HCV. Genetic variation observed in the nucleotide and the amino acid sequences between the two groups resembles that in the NS3 region of the genome between Japanese encephalitis virus and West Nile fever virus. Polypeptides produced inEscherichia coli carrying a clone 11–7 or a group II cDNA clone E reacted with antibodies in the blood of 12 or 4 out of 14 individual chronic NANBH patients, respectively. Our data clearly indicate the existence of a second group of HCV.     

Mutliple hepatitis viruses in multiple attacks of acute viral hepatitis.

We evaluated the causes of 30 episodes of acute viral hepatitis in 13 patients who had multiple attacks. Two (seven per cent) of 30 bouts were caused by hepatitis A virus, and 12 (40%) by hepatitis B virus. No patient, however, had more than one attack with the serologic characteristics of Type A or Type B disease. Thus, there were 16 bouts (53 per cent) not attributable to either of the two recognized hepatitis viruses. None of these "non-A, non-B" episodes, evaluated for infectious mononucleosis and cytomegalovirus infection, could be ascribed to either. From this evidence, therefore, it appears that the clinical syndrome of viral hepatitis is produced not only by the two viruses (hepatitis A virus and hepatitis B virus) recognized since the 1940's but also, in all probability, by two non-A, non-B agents.     

An overview of the diagnostic tools

Prions are unconventional infectious agents that cause fatal neurological illnesses such as Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy, and scrapie. Variant CJD can occur via blood transfusions. However, as no screening assay is available, uncertainties remain over the prevalence of vCJD in asymptomatic blood donors. Development of a diagnostic assay is therefore a primary objective. Little is known about the nature, distribution and level of infectivity in human blood and we have to rely on assumptions made from animal models. Ideally, two types of assays are required: a rapid high-throughput assay to routinely screen all blood donations and a confirmatory assay to ensure that all positive results from initial screening are true positives. Key event in prion disease is thought to be the conversion of normal cellular prion protein PrPc to a misfolded aggregated form termed PrP^TSE. This specific characteristic has been exploited to develop some tests.     

Cryoglobulinemia related to the hepatitis B and C viruses

Most cases of "essential" mixed cryoglobulinemia are due to chronic infection with the hepatitis C virus (HCV). Although cryoglobulinemia is a common finding in HCV-infected patients, it is rarely symptomatic. However, some patients develop diffuse vasculitis predominantly affecting small-caliber blood vessels, particularly those of the skin. Treatment with steroids, immunosuppressives, and more recently interferon alpha is effective in the short and medium term but fails to provide a permanent cure for the vasculitis. Cryoglobulinemia associated with hepatitis B virus (HBV) infection is less common. The HBV and HCV have closely similar epidemiological characteristics, and the few historical series of cryoglobulinemia with HBV infection reported in the literature do not allow to determine the role of coinfection with the HCV.     

Prevalence of parenterally transmitted hepatitis viruses in clinically diagnosed cases of hepatitis

Hepatitis B virus (HBV) is the most important causative agent of blood borne hepatitis in humans. Hepatitis D Virus (HDV) infection occurs either as a coinfection or superinfection in HBV carriers. Hepatitis C virus (HCV) is the major cause of transfusion non-A, non-B hepatitis and continues to be a major cause of human liver disease throughout the world. The present study was conducted on 70 clinically diagnosed cases of viral hepatitis to study the prevalence of parenterally transmitted viral hepatitis. The serum samples were tested for HBsAg, HBeAg, IgM anti-HBc, anti-HBe, anti-HCV and anti-HDV using separate ELISA kits. Of the 70 serum samples tested, 28 (40%) were positive for HBsAg out of which 3 (4.28%) were positive for HBeAg also. Five (7.1%) of the HBsAg positive cases tested positive for IgM anti-HBc also. HBsAg alone was found in 17 (24.28%) cases. The prevalence of anti-HCV was 3 (4.28%) in 70 cases. Thus early screening of clinically diagnosed cases of viral hepatitis is essential for establishing diagnosis and treatment to prevent long term sequelae.     

Delta and non-A,non-B hepatitis viruses

A review is given on the current knowledge of the hepatitis delta virus (HDV), the only hepatotropic non-A and non-B (NANB) virus characterized, although the infection it causes requires infection with hepatitis B virus (HBV). Studies in chimpanzees have provided the most data now available on the putative NANB agents. Histologic and electron microscopic changes occurring in HDV and NANB hepatitis have been shown to be comparable, and some biologic, epidemiologic and clinical features are similar. However, the lack of cross-protection between NANB and HDV hepatitis in cross-challenge transmission experiments and the lack of hybridization between HDV-RNA and nucleic acids from NANB material indicate that HDV and the putative NANB agents are minimally, if at all, related.     

An overview of Ensembl

Ensembl (http://www.ensembl.org/) is a bioinformatics project to organize biological information around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of individual genomes, and of the synteny and orthology relationships between them. It is also a framework for integration of any biological data that can be mapped onto features derived from the genomic sequence. Ensembl is available as an interactive Web site, a set of flat files, and as a complete, portable open source software system for handling genomes. All data are provided without restriction, and code is freely available. Ensembl's aims are to continue to "widen" this biological integration to include other model organisms relevant to understanding human biology as they become available; to "deepen" this integration to provide an ever more seamless linkage between equivalent components in different species; and to provide further classification of functional elements in the genome that have been previously elusive.     

Autoimmune hepatitis in Brazil: an overview

Autoimmune hepatitis is an immune cell-mediated chronic liver disease of unknown cause that leads, when untreated, to cirrhosis and liver failure. Importantly, this disease affects not only adults but children as well. Genetic susceptibility is clearly important and the major susceptibility factor identified up to now is the HLA-DRB1 locus, but other genes may play a role as well. HLA-DRB1 alleles present in South American patients differ from those found in patients in other parts of the world. In addition, we have recently identified two chromosomal regions where additional susceptibility factors may be found in Brazilian patients, namely, the class III MHC region and the 5q31 region where the IL-4 and IL-13 genes are located. This review discusses the current knowledge of the pathogenesis of this autoimmune disease occurring in the setting of an immune-privileged organ, the liver, and compares the data on gene polymorphisms studied in Brazil and in other parts of the world.     

An overview of the genetics of psychopathology

The suggestion that psychopathologies are in part mediated by aberrant catecholamine metabolism has resulted in one of the more rapidly growing areas of pharmacogenetics. Collectively, the studies conducted to date indicate that psychopathological conditions have multiple causes which cannot be related to single genetic or biochemical deficits. However, through multidisciplinary research integrating behavioral, genetic, and biochemical approaches, a great deal of insight may be gained concerning the causes of psychopathological disorders and the use of drug therapy to modify the course of these illnesses.D.R.P.'s research is supported in part by NIAAA Research Grant AA-03527 and by The Council for Tobacco Research Grant CTR-1243. A.C.C. is the recipient of Research Scientist Development Award AA-00029; his research is supported in part by NIAAA Research Grant AA-03527.     

Co-expression of markers for hepatitis delta and hepatitis B viruses in human liver

Delta hepatitis (HDV) infection can only occur in the presence of hepatitis B (HBV) infection, as HDV requires a coat of HBV surface antigen (HBsAg) for assembly of complete virus. A number of studies have examined the variation of HBV markers in serum and liver during establishment of HDV infection, but none has systematically examined the relationship between the two viruses in individual hepatocytes. Liver biopsies from five patients with HDV/HBV infection were stained for HBsAg, HBV core antigen (HBcAg) and hepatitis D (delta) antigen (HDAg). Double immunostaining was performed with a combination of indirect immunoperoxidase and alkaline phosphatase/antialkaline phosphatase techniques. HDV and HBV antigens were expressed in all five liver biopsies. Co-localization of HBsAg was seen in up to 39% of HDAg positive cells, and HBcAg in up to 8% of HDAg positive cells. HBcAg was detectable in approximately 9% of HBsAg positive cells, and HBsAg in approximately 12% of HBcAg positive cells. HDV can replicate without HBV but ultimately requires HBV to produce complete virus and subsequently infect other cells. In this study the majority of HDV positive cells did not appear to contain HBV markers. This might suggest delta virus replication without assembly, or possibly sequential production/assembly of the virus.