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Generation of recombinant lymphocytic choriomeningitis viruses with trisegmented genomes stably expressing two additional genes of interest

Academic Article
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Overview

authors

  • Emonet, S. F.
  • Garidou, L.
  • McGavern, Dorian
  • de la Torre, Juan

publication date

  • March 2009

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Several arenaviruses cause hemorrhagic fever disease in humans for which no licensed vaccines are available and current therapeutic intervention is limited to the off-label use of the wide-spectrum antiviral ribavirin. However, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has proven to be a Rosetta stone for the investigation of virus-host interactions. Arenaviruses have a bisegmented negative-strand RNA genome. The S segment encodes for the virus nucleoprotein and glycoprotein, whereas the L segment encodes for the virus polymerase (L) and Z protein. The ability to generate recombinant LCMV (rLCMV) expressing additional foreign genes of interest would open novel avenues for the study of virus-host interactions and the development of novel vaccine strategies and high-throughput screens to identify antiarenaviral molecules. To this end, we have developed a trisegmented (1L + 2S) rLCMV-based approach (r3LCMV). Each of the two S segments in r3LCMV was altered to replace one of the viral genes by a gene of interest. All r3LCMVs examined expressing different reported genes were stable both genetically and phenotypically and exhibited wild-type growth properties in cultured cells. Reporter gene expression in r3LCMV-infected cells provided an accurate surrogate of levels of virus multiplication. Notably, some r3LCMVs displayed highly attenuated virulence in mice but induced protective immunity against a subsequent lethal challenge with wild-type LCMV, supporting the potential development of r3LCMV-based vaccines.

subject areas

  • Animals
  • Cell Line
  • Cercopithecus aethiops
  • Cricetinae
  • Disease Models, Animal
  • Gene Expression
  • Gene Expression Regulation, Viral
  • Genome, Viral
  • Lymphocytic Choriomeningitis
  • Lymphocytic choriomeningitis virus
  • Mice
  • Phenotype
  • Virion
  • Virus Replication
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Research

keywords

  • antiviral screen
  • reverse genetic
  • viral attenuation
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Identity

PubMed Central ID

  • PMC2651270

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0900088106

PubMed ID

  • 19208813
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Additional Document Info

start page

  • 3473

end page

  • 3478

volume

  • 106

issue

  • 9

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