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A cell-based luciferase assay amenable to high-throughput screening of inhibitors of arenavirus budding

Academic Article
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Overview

authors

  • Capul, A. A.
  • de la Torre, Juan

publication date

  • December 2008

journal

  • Virology  Journal

abstract

  • Several arenaviruses cause hemorrhagic fever (HF) disease in humans for which there are no licensed vaccines, and current therapy is limited to the use of ribavirin (Rib) that is only partially effective and associated with significant side effects. In addition, compelling evidence indicates that the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Therefore, it is important to develop novel and effective anti-arenaviral drugs. The arenavirus Z protein is the driving force of arenavirus budding, and PPPY and PTAP late (L) domain motifs within Z are critical for Z-mediated budding, which involves the interaction of Z with a variety of host cellular factors. Compounds capable of inhibiting these virus-host cell interactions represent candidate anti-arenaviral drugs. The identification of these candidate compounds would be facilitated by the availability of a Z budding assay amenable to high-throughput screens (HTS). To this end, we have developed a novel assay that allows for rapid and quantitative assessment of Z-mediated budding. We provide evidence that this novel assay is amenable to HTS to identify small molecule inhibitors of Z-mediated budding, as well as to uncover cellular genes contributing to arenavirus budding.

subject areas

  • Antiviral Agents
  • Arenavirus
  • Drug Evaluation, Preclinical
  • Genes, Reporter
  • Humans
  • Luciferases
  • Lymphocytic choriomeningitis virus
  • Staining and Labeling
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Research

keywords

  • Arenavirus
  • Gaussia luciferase
  • High-throughput screen
  • Lassa fever virus
  • Virus budding
  • Z protein
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Identity

PubMed Central ID

  • PMC3799951

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2008.09.008

PubMed ID

  • 18929379
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Additional Document Info

start page

  • 107

end page

  • 114

volume

  • 382

issue

  • 1

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