Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients

doi:10.1128/JVI.75.17.8240-8250.2001

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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, inaddition to forming the viral nucleocapsid, has multiple regulatoryfunctions in host-cell transcription, apoptosis, cell transformation,and lipid metabolism and may play a role in suppressing host immuneresponse. This protein is thought to be present in the bloodstreamof the infected host as the nucleocapsid of infectious, envelopedvirions. This study provides evidence that viral particles withthe physicochemical, morphological, and antigenic properties ofnonenveloped HCV nucleocapsids are present in the plasma of HCV-infectedindividuals. These particles have a buoyant density of 1.32 to1.34 g/ml in CsCl, are heterogeneous in size (with predominanceof particles 38 to 43 or 54 to 62 nm in diameter on electron microscopy),and express on their surface epitopes located in amino acids 24to 68 of the core protein. Similar nucleocapsid-like particlesare also produced in insect cells infected with recombinant baculovirusbearing cDNA for structural HCV proteins. HCV core particles isolatedfrom plasma were used to generate anti-core monoclonal antibodies(MAbs). These MAbs stained HCV core in the cytoplasm of hepatocytesfrom experimentally infected chimpanzees in the acute phase ofthe infection. These chimpanzees had concomitantly HCV core antigenin serum. These findings suggest that overproduction of nonenvelopednucleocapsids and their release into the bloodstream are propertiesof HCV morphogenesis. The presence of circulating cores in serumand accumulation of the core protein in liver cells during theearly phase of infection may contribute to the persistence ofHCV and its many immunopathological effects in the infectedhost.

^* Corresponding author. Mailing address: Molecular Epidemiology of Enteroviruses, Institut Pasteur, 25 Rue du Dr. Roux, 75724Paris, France. Phone: 33-1-4568 8261. Fax: 33-1 4568 8780. E-mail:abudkow{at}pasteur.fr.

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