Non-A, Non-B Hepatitis: Ultrastructural Evidence for Two Agents in Experimentally Infected Chimpanzees

Shimizu, Yohko K.; Feinstone, Stephen M.; Purcell, Robert H.; Alter, Harvey J.; London, William T.

doi:10.1126/science.451589

Cited by 276 publications

(116 citation statements)

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“…These tubular structures are morphologithe liver are very low, almost undetectable, although the liver is constantly bathed in blood containing HCV. cally indistinguishable from those described in an earlier ultrastructural study of HCV-infected chimpanBoth a low rate of replication and the ability to infect (and potentially disarm) cells of the immune sys-zees; 21 however, these structures are not specific for HCV infection. As Shimizu et al note, 1 they arise in tem, 7-10 may help HCV to persist in the face of elaborate eradication strategies.…”

Section: The First Issue Is One Of Accesscontrasting

confidence: 55%

Replication of hepatitis C virus: Catching it in the act

Branch¹

1996

Hepatology

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Section: The First Issue Is One Of Accesscontrasting

confidence: 55%

Replication of hepatitis C virus: Catching it in the act

Branch¹

1996

Hepatology

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“…Data have accumulated suggesting that there might be more than one type of NANBH virus associated with blood transfusion (10). They include (i) clinical manifestations (11), (ii) electron microscopic findings of infected chimpanzee livers (12), (iii) experimental cross challenges in chimpanzees (13,14), and (iv) physicochemical properties of the agents (15). Our data suggest that HCV seroconversion is closely associated with NANBH patients whose sera display multiphasic enzyme elevations for long periods of time.…”

Section: Discussionmentioning

confidence: 75%

Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis.

Miyamura

Saito

Katayama

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

168

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A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatitis (NANBH). We have assayed for antibodies reacting with the encoded antigen in sera from posttrnnsfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. In contrast to the patients of chronic hepatitis, the antibody was barely detected in patients with a single episode of ALT elevation (1 out of 6). Of the 15 well-dermed cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11(73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented. The antibody assay thus can be used for diagnosis and blood screening for PT-NANBH.Even though donor blood is routinely screened for the hepatitis B virus (HBV) with sensitive assays, about 10% of blood transfusion recipients still develop viral hepatitis (refs. 1 and 2; T.K., unpublished data). Non-A, non-B hepatitis (NANBH) virus(es) is responsible for over 90%o of the posttransfusion hepatitis (PTH) cases and causes a serious health problem throughout the world. NANBH is much more likely to become chronic than HBV-induced hepatitis and often progresses to chronic liver disease, including liver cirrhosis (3, 4). A role for NANBH in the development of hepatocellular carcinoma has also been suggested (5, 6).The genome of a NANBH virus, termed hepatitis C virus (HCV), was cloned recently and shown to contain a positivestranded RNA molecule (7). An assay for circulating viral antibodies was developed by using an HCV antigen purified from recombinant yeast clones to capture reactive antibodies. Results obtained using this assay indicated that HCV is a major cause of transfusion-associated NANBH throughout the world as well as community-acquired NANBH in which no previous parenteral exposure to the virus could be identified (8).In this study, we assayed for HCV antibody in wellpedigreed transfusion-associated NANBH patients in Japan. The serum samples were from patients diagnosed on the basis of clinical presentation in the absence of markers indicating infection with HBV and hepatitis A virus (HAV).-The recipient sera were a series ...

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“…HCV infection in this chimpanzee were reported elsewhere. 6 Received April 30, 1995; accepted August 1, 1995. Immunofluorescence. Immunofluorescence ( Standard Thin-Section EM.…”

Section: Hpbma10-2 Hpball and Daudi Cells Infected Withmentioning

confidence: 99%

Hepatitis C virus: Detection of intracellular virus particles by electron microscop

Shimizu¹

1996

Hepatology

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titer of the virus in clinical samples and problems in SEE EDITORIAL ON PAGE 372. confirming the identity of viruslike particles.We previously reported that certain human lymphoWe previously demonstrated that a human T-cell line, cytic cell lines were susceptible to HCV infection. The HPBMa10-2 derived from HPBALL, was capable of sup-viral replication in a human T-cell line, a clone (10-2) porting a productive infection of hepatitis C virus of HPBMa derived from HPBALL, was shown to be (HCV). We subsequently found Daudi cells, a human B-productive for infectious HCV. 2,3 In addition, we recell line, to be susceptible to HCV infection. Employing cently found that Daudi cells, a human B-cell line, were these cell lines infected with HCV as well as liver ob-capable of supporting a productive infection of HCV as tained during the acute phase of hepatitis C from a chim-well. We have been able to establish long-term, persispanzee, we observed intracellular HCV particles by elec-tently infected cultures of these cell lines. Employing tron microscopy (EM). We detected viruslike particles HPBMa10-2, HPBALL, and Daudi cells, infected with with a diameter of approximately 50 nm in the cyto-HCV, as well as liver obtained from an infected chimplasmic vesicles. In Daudi cells harvested 15 days after virus inoculation, the appearance of cytoplasmic tubu-panzee, we attempted to observe intracellular HCV lar structures which we originally described for chim-particles by standard thin-section electron microscopy panzee hepatocytes in association with HCV infection (EM) and immunoperoxidase EM. sensitive assay for detecting the HCV genome by rewas carried out as we described previously, and 20 mL of verse transcription/polymerase chain reaction and undiluted plasma H77 that contained 10 6.5 50% chimpanzee assays employing recombinant HCV proteins for de-infectious doses of HCV per milliliter 5 served as inoculum. tecting antibodies to the virus have been developed. The viral replication was evaluated by detection of intracelluVisualization of complete HCV virions, however, has lar HCV RNA negative strand, a template for virion RNA been extremely difficult primarily because of the low synthesis, by reverse transcription/polymerase chain reaction using nested primers to detect the 5 noncoding region (map position 9-331) of the HCV genome. HPBMa10-2 cells harvested on day 14, HPBALL cells harvested on day 25, and tion were subjected to the current examination. The liverFrom the

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Non-A, Non-B Hepatitis: Ultrastructural Evidence for Two Agents in Experimentally Infected Chimpanzees

Cited by 276 publications

References 5 publications

Replication of hepatitis C virus: Catching it in the act

Replication of hepatitis C virus: Catching it in the act

Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis.

Hepatitis C virus: Detection of intracellular virus particles by electron microscop

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