SCIENCE@home

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

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

Published 2003 in Virology

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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-59 of 59 references · Page 1 of 1

CITED BY

Showing 1-100 of 165 citing papers · Page 1 of 2

12
Next