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Journal of Virology, December 2002, p. 12325-12334, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12325-12334.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Generation of Hepatitis C Virus-Like Particles by Use of a Recombinant Vesicular Stomatitis Virus Vector

Heather J. Ezelle, Dubravka Markovic, and Glen N. Barber*

Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida

Received 24 April 2002/ Accepted 23 August 2002

Hepatitis C virus (HCV), a major etiologic agent of hepatocellular carcinoma, presently infects approximately 400 million people worldwide, making the development of protective measures against HCV infection a key objective. Here we have generated a recombinant vesicular stomatitis virus (VSV), which expresses the HCV structural proteins, by inserting the contiguous Core, E1, and E2 coding region of HCV into the VSV genome. Recombinant VSV expressing HCV Core, E1, and E2 (VSV-HCV-C/E1/E2) grew to high titers in vitro and efficiently expressed the incorporated HCV gene product, which became fully processed into the individual HCV structural proteins. Biochemical and biophysical analysis indicated that the HCV Core, E1, and E2 proteins assembled to form HCV-like particles (HCV-LPs) possessing properties similar to the ultrastructural properties of HCV virions. Mice immunized with VSV-HCV-C/E1/E2 generated cell-mediated immune responses to all of the HCV structural proteins, and humoral responses, particularly to E2, were also readily evident. Our data collectively indicate that engineered VSVs expressing HCV Core, E1, and E2 and/or HCV-LPs represent useful tools in vaccine and immunotherapeutic strategies designed to address HCV infection.

* Corresponding author. Mailing address: Rm. 511 Papanicolaou Building, 1550 NW 10th Ave. [M710], University of Miami School of Medicine, Miami, FL 33136. Phone: (305) 243-5914. Fax: (305) 243-5885. E-mail: gbarber{at}med.miami.edu.

Journal of Virology, December 2002, p. 12325-12334, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12325-12334.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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