Biomedical subjects

J L Gerin

Publications and source records attributed to J L Gerin.

At least 109 records · Page 6Linked to original sources

PubMed1988

A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta.

On the basis of the complete nucleotide sequence of the single-stranded, covalently closed circular hepatitis delta virus RNA genome (K.-S. Wang, Q.-L. Choo, A. J. Weiner, J.-H. Ou, R. C. Najarian, R. M. Thayer, G. T. Mullenbach, K. J. Denniston, J. L. Gerin, and M. Houghton, Nature [London] 323:508-514, 1986 [Author's correction, 328:456, 1987]), five long open reading frames (ORFs) encoding polypeptides containing a methionine proximal to the amino terminus were expressed in bacteria. Only polypeptides encoded by the antigenomic ORF5 cross-reacted with antisera obtained from patients with hepatitis delta virus infections. Immunological analysis of viral extracts and the recombinant ORF5 polypeptides synthesized in bacteria and yeast cells revealed that ORF5 encodes the immunogenic epitope(s) shared by both hepatitis delta viral polypeptides p27 delta and p24 delta and probably represents the complete structural gene for p27 delta and p24 delta. We also present evidence that ORF5 encodes the hepatitis delta antigen, an antigen originally found in the nuclei of hepatocytes of infected individuals (M. Rizzetto, M. G. Canese, S. Arico, O. Crivelli, F. Bonino, C. G. Trepo, and G. Verme, Gut 18:997-1003, 1977). A comparison of the primary structure of the predicted hepatitis delta antigen polypeptides with that of the core antigen of the hepatitis B virus shows that these polypeptides are very dissimilar.

Amino Acid Sequence↗

PubMed1987

Hepatitis delta (delta) cDNA clones: undetectable hybridization to nucleic acids from infectious non-A, non-B hepatitis materials and hepatitis B DNA.

Hepatitis Delta (delta) cDNA clones were hybridized to RNA extracted from livers of chimpanzees infected with the blood-borne Non-A, Non-B hepatitis (NANBH) agent(s) and to total nucleic acids extracted from chimpanzee plasma containing a high titer of these NANBH agent(s). Since no hybridization was observed, the data suggests that the hepatitis Delta viral genome is not closely related to the genome(s) of the NANB agent(s). Our studies, in which the Hepatitis B virus genomic DNA was hybridized to hepatitis Delta cDNA clones, also confirm and extend previous studies [Hoyer et al, 1983], which report a lack of detectable homology between the hepatitis Delta genome and HBV DNA.

Animals↗

PubMed1987

Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults.

We prospectively followed up 821 adults with acute viral hepatitis hospitalized at the Athens Hospital for Infectious Diseases between May 1981 and May 1983. Radioimmunoassays for the detection of serologic markers of hepatitis A virus, hepatitis B virus, and hepatitis delta virus, and molecular hybridization techniques for the detection of serum hepatitis B virus deoxyribonucleic acid and hepatitis delta virus ribonucleic acid were used. Based on the results of an enzyme immunoassay for the detection of immunoglobulin M antibody to hepatitis B core antigen (Corzyme-M), 563 cases were diagnosed as acute hepatitis B and 45 as acute hepatitis superimposed on hepatitis B surface antigen carriage. Development of the hepatitis B surface antigen carrier state was observed in only 1 (0.2%) of the 507 cases with acute hepatitis B that were followed. In contrast, hepatitis B surface antigen persisted in all the latter cases. Acute hepatitis superimposed on hepatitis B surface antigen carriage was attributed to hepatitis A virus superinfection in 2 (4.4%), hepatitis delta virus superinfection in 22 (48.9%), reactivation of chronic type B hepatitis in 12 (26.7%), seroconversion from hepatitis B e antigen-positive to anti-hepatitis B e antibody-positive in 2 (4.4%), presumed superinfection by non-A, non-B agent(s) in 6 (13.4%), and the first clinical manifestation of chronic active hepatitis in 1 (2.2%) case. These data show that acute clinical hepatitis B in adults seems to be a self-limited disease and rarely leads to the development of the carrier state in this epidemiologic setting and hepatitis delta virus superinfection and spontaneous reactivation of chronic hepatitis B are the principal causes of acute hepatitis superimposed in hepatitis B surface antigen carriers in an area with a moderately high prevalence of hepatitis B virus infections.

Acute Disease↗

PubMed1987

Hepatocarcinogenicity of the woodchuck hepatitis virus.

During investigations of the evolution of experimental laboratory infections of woodchucks (Marmota monax) with the woodchuck hepatitis virus (WHV), eight hepatocellular carcinomas (HCC) were observed, six in newborns and two in young adult animals, all within 17-36 months after infection. The absence of an external cocarcinogenic effect in the well-monitored woodchucks indicates the carcinogenicity of WHV and suggests the same for the genetically and biologically similar human hepatitis B virus (HBV). Laboratory infections of woodchucks with two strains of WHV, not reported here in detail, resembled human and chimpanzee HBV infections histologically and serologically. In these studies, eight woodchucks became carriers of surface antigen of WHV for greater than 1 year. All eight woodchucks developed HCC, indicating a 100% risk of HCC in experimentally infected chronic WHV antigen carriers, which is analogous to the high risk of HCC in human hepatitis B surface antigen carriers. Histologically, the absence of cirrhosis in the examined pericarcinomatous tissue permits recognition of gradual transition from normal parenchyma to neoplastic nodules to HCC of rising anaplasia, indicating a continuum of increasingly more malignant neoplastic stages, as known for chemical carcinogenesis. The HCC developed in carrier woodchucks infected as newborns with only minor, if any, hepatitic changes but is associated with antigen-carrying hepatocytes and sometimes with hyperplastic nodules. This stage was preceded in infected adults by an early, acute, weeks-long hepatitis coinciding with the appearance of surface antigen. These findings are also analogous to typical HBV infection in human newborns and young adults, respectively. At the time of HCC development in all animals with adequate histologic material, an acute recent necroinflammation appeared around the tumor, associated with abnormal hematopoietic cells around and within the tumor. A promoting role in carcinogenesis of this necroinflammation of yet unestablished pathogenesis is being postulated, to be confirmed by determination of the status of the WHV DNA in the HCC and by prospective histologic study of the inflammatory reaction.

Animals↗

PubMed1987

Titration of the infectivity of hepatitis D virus in chimpanzees.

The infectivity of hepatitis D virus (HDV) was evaluated by intravenous inoculation of chimpanzees. HDV was present in the inoculum at a titer of 10(11) chimpanzee infectious doses (CID). In contrast, the titer of hepatitis B virus (HBV) in the same inoculum was 10(6) CID. All HBV-infected chimpanzees inoculated with less than or equal to 10(-11) dilutions of the HDV-positive plasma were superinfected; an animal receiving a 10(-12) dilution did not develop markers of HDV replication in serum or liver. All HDV-infected chimpanzees had marked elevations of serum alanine aminotransferase activities. The incubation period from exposure to development of hepatitis was inversely related to the dose of HDV inoculum, although the severity and duration of hepatitis were independent of it. All animals recovered and rapidly developed antibody to hepatitis D antigen.

Alanine Transaminase↗

PubMed1987

Safety and immunogenicity of a purified hepatitis B virus vaccine prepared by using recombinant DNA technology.

Forty healthy adult males were given a 20-micrograms intramuscular dose of either a new recombinant hepatitis B virus (HBV) vaccine produced in mammalian cells (rHBsAg) or the currently licensed HBV vaccine derived from human plasma (HEPTAVAX-B), and booster doses were administered one month and six months later. The percentage of vaccinees who seroconverted on the 10th and 30th days after the first vaccination was higher for the rHBsAg vaccinees than for the recipients of plasma-derived vaccine (rHBsAg: 10% on day 10 and 70% on day 30; HEPTAVAX-B: 0% and 25%, respectively). The only statistically significant difference in titers of antibody to HBV surface antigen was noted 30 days after the first vaccination. Both vaccines induced a shift in antibody from the 19S to the 7S fraction and a specific antibody response to the a determinant. The rHBsAg vaccine was not associated with significant reactogenicity or toxicity and was somewhat more immunogenic than the currently licensed product.

Adult↗

PubMed1987

A human monoclonal antibody that recognizes viral polypeptides and in vitro translation products of the genome of the hepatitis D virus.

Peripheral blood lymphocytes from a patient chronically infected with hepatitis D virus (HDV) were immortalized by Epstein-Barr virus transformation. Two stable monoclonal cell lines, derived from the same parent culture, were established and produced antibodies of the IgG isotype that were specific for the hepatitis delta antigen (HDAg). Both monoclonal antibodies (MAbs) recognized the major HDAg polypeptides of 24 kilodaltons and 27 kilodaltons that were previously detected by polyclonal antibodies to HDAg in both liver and serum from HDV-infected humans, chimpanzees, and woodchucks. This result indicates that the major polypeptides of HDAg share common epitopes. The MAbs also reacted with minor polypeptides of lower molecular weight, which were present in infected liver. In vitro translation products of HDV-specific RNA from infected liver were also detected by the MAbs; these polypeptides were 24 kilodaltons and 27 kilodaltons, respectively, and comigrated with liver- or serum-derived HDAg. In contrast, HDV RNA isolated from virions in serum was not translated into HDAg polypeptides in the in vitro system.

Animals↗

PubMed1987

Lymphoid cells in the spleens of woodchuck hepatitis virus-infected woodchucks are a site of active viral replication.

Lymphoid cells were purified from the spleens of 15 woodchucks and examined for the presence of woodchuck hepatitis virus (WHV). Lymphoid cells from the spleens of eight of eight chronically infected animals contained high levels of WHV RNA and DNA. A 100-fold lower level of WHV DNA was found in the spleen from one of five animals that had recovered from acute WHV infections 2 years before this analysis. No WHV nucleic acids were observed in either of two uninfected animals. WHV DNA patterns in the lymphoid cells from the spleens of the chronically infected animals, which included the presence of single-stranded DNA and RNA-DNA hybrid molecules, were identical to those observed in WHV-infected liver. WHV DNA in these cells was present in intact, 27-nm core particles which also contained the endogenous DNA polymerase activity. These results indicate that the spleen is a site of active WHV DNA replication and is most likely a major source of WHV-infected cells in the circulating lymphoid cell population.

Animals↗

PubMed1987

Relation between non-A, non-B and delta hepatitis: studies with monoclonal antibodies.

To further investigate the specificity of the monoclonal antibodies (48-1 and S-1) associated with NANB hepatitis, extensive IF studies were carried out on liver biopsy specimens from chimpanzees with experimental hepatitis A, B, NANB, or D, or from normal chimpanzees. Both 48-1 and S-1 antibodies reacted in the same manner with liver biopsy specimens from 47 of 50 (94%) chimpanzees with acute or chronic NANB hepatitis and 15 of 18 (83%) chimpanzees with type D hepatitis. Examinations of serial liver biopsy specimens revealed that the duration of expression of the antigen reacting with the antibodies in hepatocytes of chimpanzees infected with NANBV appeared to be longer than that of chimpanzees infected with HDV. By thin section EM, the presence of the microtubular aggregates, identical to those previously described for chimpanzees with NANB hepatitis and shown by immuno EM to react with the antibodies, was noted in hepatocytes during the acute phase of hepatitis D. The antibodies did not react with liver biopsy specimens from chimpanzees acutely or chronically infected with HBV, or HAV, or from normal chimpanzees. The present results confirm our previous observations with the 48-1 and S-1 antibodies. Furthermore, the finding that these two antibodies were also associated with hepatitis D would support the possibility that NANB agents and the HDV may have a similar nature or may elicit a similar host response.

Animals↗

PubMed1987