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Updated: Aug 14, 2026
Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Arenavirus extinction through lethal mutagenesis
1Department of Neuropharmacology IMM-6, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. juanct@scripps.edu
Abstract:
Viral hemorrhagic fevers represent serious human public health problems causing devastating and often lethal disease. Several hemorrhagic fevers are caused by arenaviruses including Lassa fever virus (LFV) and the South American viral hemorrhagic fevers (SAHF). In recent years, increased air travel between Africa and other areas has led to the importation of LFV into the US, Europe, Japan, and Canada. This has raised awareness about arenaviruses as potential emerging viruses. Moreover, because of its severe morbidity and high mortality, and transmissibility from human to human, weaponized forms of LFV poses a real threat as agent of bioterrorism. No licensed vaccine is available in the US, and currently there is not efficacious therapy to treat these infections. Therefore, the importance of developing novel effective antiviral drugs to combat HF arenaviruses, for which the prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV) provides us with an excellent model system. Recent findings have shown that LCMV multiplication both in cultured cells and in vivo is highly susceptible to the mutagenic agent 5-fluorouracil (FU). FU-mediated extinction of LCMV was associated with only modest increases in virus mutation frequencies, but did not significantly affect virus replication and transcription, or virus particle formation. These findings indicate that, as with other riboviruses, lethal mutagenesis is effective also against LCMV raising the possibility of using this novel antiviral strategy to combat pathogenic arenaviruses.
Insights
Lethal mutagenesis using 5-fluorouracil (FU) effectively reduces lymphocytic choriomeningitis virus (LCMV) replication. This antiviral strategy shows promise for combating dangerous arenaviruses like Lassa fever virus.
Area of Science:
- Virology
- Infectious Diseases
- Antiviral Research
Background:
- Viral hemorrhagic fevers (VHFs) are severe, often fatal diseases caused by arenaviruses, including Lassa fever virus (LFV).
- Increased global travel has led to LFV importation, raising concerns about emerging viral threats and bioterrorism potential.
- Current treatment options for VHFs are limited, with no licensed vaccines available in the US.
Purpose of the Study:
- To investigate the efficacy of lethal mutagenesis as a novel antiviral strategy against arenaviruses.
- To evaluate the impact of 5-fluorouracil (FU) on the replication of lymphocytic choriomeningitis virus (LCMV), a prototypic arenavirus model.
Main Methods:
- Treatment of LCMV-infected cultured cells and in vivo models with the mutagenic agent 5-fluorouracil (FU).
- Assessment of viral replication, transcription, mutation frequencies, and particle formation following FU treatment.
Main Results:
- LCMV multiplication was highly susceptible to 5-fluorouracil (FU)-induced lethal mutagenesis.
- FU treatment led to viral extinction with only modest increases in virus mutation frequencies.
- Virus replication, transcription, and particle formation were not significantly affected by FU, indicating a specific lethal mutagenesis effect.
Conclusions:
- Lethal mutagenesis is an effective strategy against arenaviruses, as demonstrated with LCMV.
- This approach offers a potential new avenue for developing antiviral therapies against pathogenic arenaviruses, including Lassa fever virus.
- Further research into lethal mutagenesis could lead to novel treatments for VHFs.
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