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Journal of Virology, September 2001, p. 8240-8250, Vol. 75, No. 17
Epidémiolgie Moléculaire des
Entérovirus,1 Station Centrale de
Microscopie Electronique,3 and
Unité de Venins,5 Institut
Pasteur, 75724 Paris, and CNRS-FRE 2369, Institut de
Biologie de Lille et Institut Pasteur de Lille, 59021 Lille,4 France, and Hepatitis
Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
303332
Received 9 March 2001/Accepted 29 May 2001
One of the characteristics of hepatitis C virus (HCV) is the high
incidence of persistent infection. HCV core protein, in addition to
forming the viral nucleocapsid, has multiple regulatory functions in
host-cell transcription, apoptosis, cell transformation, and lipid
metabolism and may play a role in suppressing host immune response.
This protein is thought to be present in the bloodstream of the
infected host as the nucleocapsid of infectious, enveloped virions.
This study provides evidence that viral particles with the
physicochemical, morphological, and antigenic properties of nonenveloped HCV nucleocapsids are present in the plasma of
HCV-infected individuals. These particles have a buoyant density of
1.32 to 1.34 g/ml in CsCl, are heterogeneous in size (with predominance of particles 38 to 43 or 54 to 62 nm in diameter on electron
microscopy), and express on their surface epitopes located in amino
acids 24 to 68 of the core protein. Similar nucleocapsid-like particles are also produced in insect cells infected with recombinant baculovirus bearing cDNA for structural HCV proteins. HCV core particles isolated from plasma were used to generate anti-core monoclonal antibodies (MAbs). These MAbs stained HCV core in the cytoplasm of hepatocytes from experimentally infected chimpanzees in the acute phase of the
infection. These chimpanzees had concomitantly HCV core antigen in
serum. These findings suggest that overproduction of nonenveloped nucleocapsids and their release into the bloodstream are properties of
HCV morphogenesis. The presence of circulating cores in serum and
accumulation of the core protein in liver cells during the early phase
of infection may contribute to the persistence of HCV and its many
immunopathological effects in the infected host.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.8240-8250.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Nonenveloped Nucleocapsids of Hepatitis C Virus
in the Serum of Infected Patients
*
Corresponding author. Mailing address: Molecular
Epidemiology of Enteroviruses, Institut Pasteur, 25 Rue du Dr. Roux,
75724 Paris, France. Phone: 33-1-4568 8261. Fax: 33-1 4568 8780. E-mail: abudkow{at}pasteur.fr.
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