Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Lethal mutagenesis of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV)

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Ruiz-Jarabo, C. M.
  • Ly, C.
  • Domingo, E.
  • de la Torre, Juan

publication date

  • March 2003

journal

  • Virology  Journal

abstract

  • Passage of the prototypic arenavirus lymphocytic choriomenigitis virus (LCMV) in cultured cells in the presence of the mutagenic agent 5-fluorouracil (FU) resulted in efficient and systematic virus extinction under conditions that did not significantly affect cell survival. FU-mediated extinction of LCMV was associated with 3.6- to 10-fold increases in the mutation frequencies for the three viral genes examined, but with only very modest effects on virus replication and transcription during a single round of infection. Likewise, FU did not affect expression of a LCMV minigenome. In contrast, the well documented antiviral effect of ribavirin against LCMV was not associated with significant increases in virus mutation frequencies, but rather with a dramatic inhibition of both viral RNA synthesis and LCMV minigenome expression. Mutagen induced viral extinction has been recently reported for positive strand RNA viruses polio and foot-and-mouth disease, and the lentivirus HIV-1. Our findings indicate that lethal mutagenesis can be effective also against LCMV, a negative strand RNA virus. Moreover, FU treatment prevented the establishment of LCMV persistent infection in mice deficient in B and T cells, suggesting the feasibility in vivo of lethal mutagenesis as a novel antiviral strategy.

subject areas

  • Animals
  • Antiviral Agents
  • Arenaviridae Infections
  • B-Lymphocytes
  • Cell Line
  • Cricetinae
  • DNA-Binding Proteins
  • Fluorouracil
  • Gene Expression
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Knockout
  • Mutagenesis
  • RNA, Viral
  • Receptors, Interferon
  • Ribavirin
  • T-Lymphocytes
  • Transfection
  • Virus Replication
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1016/s0042-6822(02)00046-6

PubMed ID

  • 12706088
scroll to property group menus

Additional Document Info

start page

  • 37

end page

  • 47

volume

  • 308

issue

  • 1

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support