Generation of hepatitis C virus-like particles by use of a recombinant vesicular stomatitis virus vector

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

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12325-12334
Number of pages10
JournalJournal of virology
Volume76
Issue number23
DOIs
StatePublished - Dec 2002

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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