The Natural History of Infection with Hepatitis C Virus (HCV) in Chimpanzees: Comparison of Serologic Responses Measured with First- and Second- Generation Assays and Relationship to HCV Viremia

Farci, Patrizia; London, William T.; Wong, Doris C.; Dawson, George J.; Vallari, D S; Engle, Ronald E.; Purcell, Robert H.

doi:10.1093/infdis/165.6.1006

Cited by 90 publications

(40 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antibodies to HCV (anti-HCV) were determined in the human plasmas from patient H with a commercially available second-generation ELISA (Ortho Diagnostic). In addition, antibodies to six target sequences derived from the structural [nucleocapsid, envelope 1 (El)] and nonstructural (NS) regions (NS3, NS4, and NS5) of the prototype HCV-1 were measured by David Chien (Chiron) using a strip immunoblot assay (RIBA TM; Chiron), as described (23 (24) and the other from the E1/E2 region of the HCV genome (10). Total RNA was extracted from 100 jil of the serum or plasma sample by the guanidiniumphenol-chloroform method, as reported (8).…”

Section: Methodsmentioning

confidence: 99%

Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.

Farci

Alter

Wong

et al. 1994

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

457

320

View full text Add to dashboard Cite

Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B hepatitis and is a major cause of chronic liver disease and hepatocellular carcinoma. Development ofan effective vaccine would be the most practical method for prevention of the infection, but whether infection with HCV elicits protective immunity in the host is unclear. Neutralization of HCV in vitro was attempted with plasma of a chronically infected patient, and the residual infectivity was evaluated by inoculation of eight seronegative chimpanzees. The source of HCV was plasma obtained from a patient during the acute phase of posttransfsion non-A, non-B hepatitis, which had previously been titered for infectivity in chimpanzees. Neutralization was achieved with plasma obtained from the same patient 2 yr after the onset of primary infection but not with plasma obtained 11 yr later, although both plasmas contained antibodies against nonstructural and structural (including envelope) HCV proteins. Analysis of sequential viral isolates from the same patient revealed significant genetic divergence as early as 2 yr after infection. However, the HCV recovered from the patient 2 yr after the infection had a striking sequence similarity with the HCV recovered from one of the chimpanzees inoculated with the acute-phase virus, suggesting that the progenitor of the new strain was already present 2 yr earlier. This evidence, together with the different sequences of HCV recovered from the chimpanzees that received the same inoculum, confirms that HCV is present in vivo as a quasispecies. These results provide experimental evidence in vivo that HCV infection elicits a neutralizing antibody response in humans but suggest that such antibodies are isolate-specific. This result raises concerns for the development of a broadly reactive vaccine against HCV.

show abstract

Section: Methodsmentioning

confidence: 99%

Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.

Farci

Alter

Wong

et al. 1994

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

457

320

View full text Add to dashboard Cite

show abstract

“…Other than humans, the only animal species that has been shown to be reproducibly susceptible to virus challenge is the chimpanzee (Pan troglodytes) (3,4). Chimpanzees may also be infected by inoculation of synthetic, genome-length viral RNA directly into the liver (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Chronic hepatitis associated with GB virus B persistence in a tamarin after intrahepatic inoculation of synthetic viral RNA

Martin

Bodola

Sangar

et al. 2003

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

View full text Add to dashboard Cite

Progress in understanding the pathogenesis of hepatitis C virus (HCV) has been slowed by the absence of tractable small animal models. Whereas GB virus B (GBV-B, an unclassified flavivirus) shares a phylogenetic relationship and several biologic attributes with HCV, including hepatotropism, it is not known to cause persistent infection, a hallmark of HCV. Here, we document persistent GBV-B infection in one of two healthy tamarins (Saguinus oedipus) inoculated intrahepatically with infectious synthetic RNA. High-titer viremia (10 8 to 10 9 genome equivalents per ml) and transiently elevated serum alanine transaminase activities were present from weeks 4 to 12 postinoculation in both animals. However, whereas GBV-B was eliminated from one animal by 20 weeks, the second animal remained viremic (10 3 to 10 7 genome equivalents per ml) for >2 years, with alanine transaminase levels becoming elevated again before spontaneous resolution of the infection. A liver biopsy taken late in the course of infection demonstrated hepatitis with periportal mononuclear infiltrates, hepatocellular microvesicular changes, cytoplasmic lipid droplets, and disordered mitochondrial ultrastructure, findings remarkably similar to chronic hepatitis C. GBV-B-infected hepatocytes contained numerous small vesicular membranous structures resembling those associated with expression of HCV nonstructural proteins, and sequencing of GBV-B RNA demonstrated a rate of molecular evolution comparable to that of HCV. We conclude that GBV-B is capable of establishing persistent infections in healthy tamarins, a feature that substantially enhances its value as a model for HCV. Mitochondrial structural changes and altered lipid metabolism leading to steatosis are conserved features of the pathogenesis of chronic hepatitis caused by these genetically distinct flaviviruses.

show abstract

“…1,2 Since then, ELISA assays have considerably improved, and the second-or third-generation tests available today are both highly sensitive and specific. [3][4][5][6] Nevertheless, second-or third-generation immunoblot tests are still used for confirmation in most laboratories. 7,8 The detection of HCV antibodies in serum does not provide information on the replicative status of HCV, a parameter that can be useful in the management of infected patients.…”

mentioning

confidence: 99%

What strategy should be used for diagnosis of hepatitis C virus infection in clinical laboratories?

et al. 1998

View full text Add to dashboard Cite

The aim of this study was to determine a cost-effective strategy for the diagnosis of hepatitis C virus ( The diagnosis of hepatitis C virus (HCV) infection is based on the detection of anti-HCV antibodies in serum, generally by means of enzyme-linked immunosorbent assays (ELISA). Two different settings must be considered: 1) Blood banks routinely perform anti-HCV testing in blood donors to identify potentially infectious donations and to avoid posttransfusion HCV infection; 2) clinical laboratories routinely search for anti-HCV antibodies in patients with risk factors for parenterally acquired viral infections or clinical symptoms compatible with HCV infection to make appropriate clinical decisions, including therapeutic ones. By analogy with human immunodeficiency virus diagnosis, the French laws have been obliging to perform two different ELISA tests in the routine diagnosis of HCV infection in clinical laboratories for several years, while only one test was needed for blood screening.First-generation anti-HCV ELISAs were lacking sensitivity as well as specificity. This is why first-generation confirmatory assays based on immunoblot testing were developed and systematically used in samples positive in ELISA. 1,2 Since then, ELISA assays have considerably improved, and the second-or third-generation tests available today are both highly sensitive and specific. 3-6 Nevertheless, second-or third-generation immunoblot tests are still used for confirmation in most laboratories. 7,8 The detection of HCV antibodies in serum does not provide information on the replicative status of HCV, a parameter that can be useful in the management of infected patients. Polymerase chain reaction (PCR)-based assays have been developed and are capable of detecting minute amounts of HCV RNA in serum or plasma.The aim of this work was to determine whether a double ELISA determination and confirmation of positive ELISA results with immunoblot assays are still useful in clinical laboratories performing routine diagnosis of HCV infection. MATERIALS AND METHODSFrom January 1 to May 22, 1996, 3,014 consecutive requests for the detection of anti-HCV antibodies were sent to the virology laboratory by the various medical departments of our institution.The serum samples were routinely tested for the presence of anti-HCV antibodies with two different ELISAs: ORTHO HCV 3.0 ELISA Test System (ELISA3.0 HCV; Ortho Clinical Systems, Raritan, NJ), and MONOLISA anti-HCV New Ag (MONOLISA HCV; Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France). ELISA 3.0 detects antibodies directed to core, nonstructural (NS) 3, NS4, and NS5 HCV antigens, while MONOLISA HCV detects antibodies directed to core, NS3, and NS4 antigens. 9 Different peptides are used in the two assays. 9 The assays were perfomed according to the manufacturers' instructions, and, in each sample, the optical density (OD) ratio was calculated by dividing the sample OD by the assay control OD. Samples with an OD ratio Ն2 were considered positive, samples with an OD ratio between 1 and 2 we...

show abstract

The Natural History of Infection with Hepatitis C Virus (HCV) in Chimpanzees: Comparison of Serologic Responses Measured with First- and Second- Generation Assays and Relationship to HCV Viremia

Cited by 90 publications

References 20 publications

Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.

Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization.

Chronic hepatitis associated with GB virus B persistence in a tamarin after intrahepatic inoculation of synthetic viral RNA

What strategy should be used for diagnosis of hepatitis C virus infection in clinical laboratories?

Contact Info

Product

Resources

About