Experimental non-A, non-B hepatitis: four types of cytoplasmic alteration in hepatocytes of infected chimpanzees

Pfeifer, U; Thomssen, R.; Legier, K.; Böttcher, Urte F.; Gerlich, Wolfram H.; Weinmann, E.; Klinge, O

doi:10.1007/bf02899184

Cited by 140 publications

(58 citation statements)

References 6 publications

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“…3 shows the antibody-reactive microtubular aggregates observed by standard thin-section EM. These were morphologically identical to those originally described by Pfeifer et al (1980) for chimpanzee NANBH.…”

Section: Methodssupporting

confidence: 80%

“…Immunoelectron microscopy (IEM) revealed that both MAbs bound to the same hepatocyte structure, the microtubular aggregates which have previously been reported to be associated with NANBH (Pfeifer et al, 1980). Recently, we found that these MAbs also react with liver tissues from hepatitis D virus (HDV)-infected chimpanzees (Shimizu et al, 1986).…”

Section: Introductionmentioning

confidence: 78%

“…2, the reaction products, indicating antibody binding, were localized to microtubular aggregates in the hepatocyte cytoplasm. Cytoplasmic tubular structures, known as type III alterations (Pfeifer et al, 1980), were not stained. Fig.…”

Section: Methodsmentioning

confidence: 95%

“…Antigen material used for immunization was prepared from a liver homogenate from chimpanzee 34, which had been inoculated with the F strain of NANBH virus (Shimizu et al, 1979), and had developed histological evidence of hepatitis, including intrahepatocytic formation of characteristic ultrastructures, i.e. tubular structures, microtubular aggregates and sponge-like inclusions (Pfeifer et al, 1980). This chimpanzee died 8 weeks after inoculation, and after autopsy its liver was used to make the antigen preparation.…”

Section: Methodsmentioning

confidence: 99%

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Production of Antibodies Directed against Microtubular Aggregates in Hepatocytes of Chimpanzees with Non-A, Non-B Hepatitis

Maeda

Honda²,

Hanawa³

et al. 1989

Journal of General Virology

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SUMMARYWe have previously used Epstein-Barr virus transformation to establish two clonal lymphoblastoid cell lines (48-1 and S-I) producing monoclonal antibodies against microtubular aggregates that appear in the hepatocytes of chimpanzees with non-A, non-B hepatitis (NANBH). To obtain additional antibodies directed against the same structure, the mouse hybridoma method was employed. Partially purified microtubular aggregates were prepared from liver homogenates of a chimpanzee with NANBH and used as the immunogen. Hybridoma cultures were first screened by radioimmunoassay against the partially purified antigen and secondly by immunofluorescence (IF) using liver sections from a chimpanzee with NANBH. Twenty-seven cultures exhibited positive IF reactions similar to those observed with the original antibodies, 48-1 and S-I, and were cloned by limiting dilution. The specificities of the monoclonal antibodies were tested by IF on liver biopsy specimens from chimpanzees with hepatitis A, B, D or NANBH and from normal chimpanzees. All the antibodies proved to be IgG. Immunoelectron microscopy revealed that all 27 antibodies bound to the same structure, the microtubular aggregates, in hepatocytes of chimpanzees with NANBH. To determine the size of the antigen polypeptide recognized by these antibodies, polyacrylamide gel electrophoresis and Western blot assays were performed. Nine of the 27 antibodies specifically reacted with a single polypeptide of Mr 44K (p44). The remaining 18 antibodies detected no antigen polypeptide on the filters. The anti-p44 antibodies were then tested using cross-competition assays with lzSI-labelled antibodies, and were found to be classifiable into three groups. In addition, the results indicate that at least three distinct epitopes are located on p44: epitope A recognized by group 1, epitope B recognized by group 2 and epitope C recognized by group 3.

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Section: Methodssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

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Production of Antibodies Directed against Microtubular Aggregates in Hepatocytes of Chimpanzees with Non-A, Non-B Hepatitis

Maeda

Honda²,

Hanawa³

et al. 1989

Journal of General Virology

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“…4A). They are also known as type I, II, and IV alterations, respectively (17). These structures were initially thought to be specific for HCV infection, but were later found in livers of HDV-infected chimpanzees as well.…”

Section: Ultrastructural Alterations In Hepatocytesmentioning

confidence: 99%

Ultrastructural Alterations and Expression of Cytoplasmic Antigen 48‐1 in Hepatocytes in Association with Hepatitis C Virus Infection

Shimizu

1992

Microbiology and Immunology

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Hepatitis type C is an important disease of humans ; it is responsible for more than 90% of the cases of posttransfusion non-A, non-B hepatitis (6,14). The etiologic agent of this disease, however, remained elusive for almost two decades, although the viral nature of the disease had been demonstrated already in 1978 by inoculating the serum or plasma from the patients into chimpanzees (1, 29). In 1989, the genome of the virus was finally discovered by the recombinant cDNA approach and the agent was termed hepatitis C virus (HCV) (5). HCV was revealed to contain a plus-strand RNA of about 10 kilonucleotides with one large open reading frame encoding a protein of 3010 amino acids (7, 13, 31) and comparative sequence analysis indicated that the virus is distantly related to the flaviviruses and pestiviruses (16). A sensitive assay for detecting HCV RNA by reverse transcription/polymerase chain reaction (RT/PCR) (32) and immunodiagnostic assays for antibodies against recombinant HCV proteins have been developed (14). The results from the serological assays indicated that most cases of hepatocellular carcinoma in Japan (19), Italy (8), and Spain (4) were associated with HCV infection.Before the emergence of these assays, chimpanzees (Pan troglodytes) were used for the characterization of the etiologic agent as the only reliable animal model for non-A, non-B hepatitis. The studies with chimpanzees have provided evidence that the virus is probably enveloped (9) and is approximately 30-60 nm in diameter (10). Additional research, however, has been hampered because of the limited availability of chimpanzees and the relatively low titer of the virus in clinical samples. To date, little is known about the replication and pathogenesis of this virus and the virion has not yet been visualized with certainty.Previously, my colleagues and I reported the presence of characteristic ultrastructural alterations (cytoplasmic tubular structures), detected by electron microscopy (EM) (22), and induction of a cytoplasmic antigen, detected by immunofluorescence staining (IF) with a monoclonal antibody (48-1) (23), in the hepatocytes of chimpanzees infected with non-A, non-B hepatitis virus (now HCV). These findings were initially thought to be specific for HCV infection, but were later found 911

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Manipulation of Centrosomes and the Microtubule Cytoskeleton during Infection by Intracellular Pathogens

Scaplehorn

Way

2004

Centrosomes in Development and Disease

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Experimental non-A, non-B hepatitis: four types of cytoplasmic alteration in hepatocytes of infected chimpanzees

Cited by 140 publications

References 6 publications

Production of Antibodies Directed against Microtubular Aggregates in Hepatocytes of Chimpanzees with Non-A, Non-B Hepatitis

Production of Antibodies Directed against Microtubular Aggregates in Hepatocytes of Chimpanzees with Non-A, Non-B Hepatitis

Ultrastructural Alterations and Expression of Cytoplasmic Antigen 48‐1 in Hepatocytes in Association with Hepatitis C Virus Infection

Manipulation of Centrosomes and the Microtubule Cytoskeleton during Infection by Intracellular Pathogens

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