Review of infectivity studies in nonhuman primates with virus-like particles associated with MS-1 hepatitis

Je, Maynard; Lorenz, Douglas E.; Dw, Bradley; Sm, Feinstone; Dh, Krushak; Lf, Barker; Rh, Purcell

doi:10.1097/00000441-197507000-00012

Cited by 45 publications

(15 citation statements)

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“…[I]. This particle, now officially accepted as the hepatitis A virus (HAV) [2], measures 27-32 nm in diameter and is mor phologically similar to members of the families Picornaviridae [3] and Parvoviridae [4], Studies of the biochemical characteristics of HAV have been hampered by the absence of an in vitro system for virus propagation and by the difficulty in obtaining large quantities of virus from man [5] or experimentally infected animals [6], The availability of high-titered HAV in fecal specimens from 3 patients with naturally acquired hepatitis A provided an opportunity to per form such a study. …”

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confidence: 99%

The Polypeptides of Hepatitis A Virus

et al. 1978

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Hepatitis A virus was purified from fecal specimens obtained from 3 patients with naturally acquired hepatitis A, by a process of differential centrifugation, chloroform extraction, column chromatography, and isopycnic ultracentrifugation. Analysis of purified virus by discontinuous SDS-PAGE revealed three major polypeptides with molecular weights of 34,000, 25,500, and 23,000 daltons. These polypeptides appear to be specific for hepatitis A virus and have similar molecular weights to three of the four major polypeptides reported for members of the genus Enterovirus within the family Picornaviridae.

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confidence: 99%

The Polypeptides of Hepatitis A Virus

et al. 1978

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“…All 5 hepatitis viruses, A, B, C, D, and E, are able to infect chimpanzees, and this model has been essential for the development of the currently licensed vaccines for hepatitis A and B. 6,[15][16][17][18][19] As the only animal model for the study of HCV, the chimpanzee has proven valuable for the study of viral transmission, 6,7,20 establishment of duration of viremia, 7,21 and identification of the physiochemical properties of HCV such as its size 22,23 and inactivation by formalin, 24,25 heat, 26 ultraviolet light, 26,27 and lipid solvents. 28,29 Importantly, HCV-infected chimpanzees provided material for isolation and characterization of the HCV genome, 8 and have been crucial for testing the infectivity of HCV clones.…”

Section: The Chimpanzee Modelmentioning

confidence: 99%

Bad time for Bonzo? Experimental models of hepatitis C virus infection, replication, and pathogenesis

2001

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Hepatitis C virus (HCV)-induced chronic hepatitis with concomitant cirrhosis and hepatocellular carcinoma is now the leading cause of liver transplantation in the United States. 1 There are currently nearly 3 million HCV carriers in the U.S. (ϳ2% of the population) and an estimated 170 million people worldwide. In 20% of patients, HCV infection is naturally cleared after several months, 2-4 but the majority of patients are chronic carriers who, in addition to being the source for most new infections, can progress to chronic active hepatitis with cirrhosis and/or hepatocellular carcinoma. Despite the increasing prevalence of HCV infection and its potentially grave clinical consequences, the only licensed therapy for chronic hepatitis is interferon ␣, either alone or in combination with ribavirin. This therapy is expensive, not effective in all HCV patients, and laden with significant side effects. 5 Unfortunately, the development of innovative treatment alternatives for HCV-infected patients has been impeded by the lack of in vitro and in vivo systems suitable for the study of HCV infection, replication, and pathogenesis.Since the successful transmission of hepatitis C to chimpanzees in 1978 6,7 and the molecular cloning of HCV as its etiologic agent in 1989, 8 the hepatitis C virus has been extensively studied and characterized at the molecular level. The virus is an enveloped flavivirus whose genome is a 9.6-kb, single-stranded RNA with positive polarity consisting of a 5Ј nontranslated region (NTR), a large open reading frame encoding all virus-specific proteins, and a 3Ј NTR. The structural proteins (C, E1, and E2) are located at the N-terminus of the polyprotein, while the virus-specific RNA polymerase and other nonstructural proteins are encoded in the remainder. 4 The enzymology of the viral replication proteins has been studied in detail and it is known that HCV RNA replication is error prone leading to the continuous generation of viral variants. Indeed, different quasispecies have been isolated from the same patient at different points in time, and have indicated the presence of multiple viral sequences located in the hypervariable region of the E1 and E2 genes. 9-11 While this dynamic variation may be important for the establishment and maintenance of persistent infection, its actual significance has been difficult to study with current technology. HCV REPLICATION IN CELL CULTUREThe investigation of many critical questions in the field of HCV research would benefit greatly by successfully achieving full replication of HCV in an experimental system. Continuous hepatoma, B-cell and T-cell lines, primary hepatocytes from humans and chimpanzees, and peripheral blood mononuclear cells have all been reported to support HCV replication. 12 Unfortunately, none has been robust enough to permit classic virologic, biochemical or genetic dissection of the HCV replication cycle. Thus, the mechanism of viral attachment and cellular entry and the precise intracellular steps in HCV-RNA replication, virus assembly, and...

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“…Host range Natural: Man; potentially chimpan zees and other higher primates [34]. Experimental In vivo: Chimpanzees [35]; marmo sets [36]. In vitro: Primary cultures of marmo set liver [33]; fetal rhesus monkey kidney [33]; Alexander hepatoma cells [37]; Vero cells [6]; African green monkey kidney cells [38]; HEL cells [22]; primary and permanent human embryonic fibroblasts [39].…”

Section: Comments and Recommendations Of The Study Groupmentioning

confidence: 99%

“…In vitro: Primary cultures of marmo set liver [33]; fetal rhesus monkey kidney [33]; Alexander hepatoma cells [37]; Vero cells [6]; African green monkey kidney cells [38]; HEL cells [22]; primary and permanent human embryonic fibroblasts [39]. Antigenic properties used for identifi cation : Neutralization of infectivity [5,35]. Detection of antigen specific for HAV by immune electron micros copy [17,18], solid-phase radioim munoassay [49], complement fixa tion [50], immune adherence assay [51], enzyme-linked immunosorbent assay [52,53], immunofluorescence [20].…”

Section: Comments and Recommendations Of The Study Groupmentioning

confidence: 99%