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Journal of Virology, September 2001, p. 8240-8250, Vol. 75, No. 17
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

P. Maillard,1 K. Krawczynski,2 J. Nitkiewicz,1 C. Bronnert,3 M. Sidorkiewicz,1 P. Gounon,3 J. Dubuisson,4 G. Faure,5 R. Crainic,1 and A. Budkowska1,*

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.


* 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.


Journal of Virology, September 2001, p. 8240-8250, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8240-8250.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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