Arenaviruses and Lethal Mutagenesis. Prospects for New Ribavirin-based Interventions

Viruses

Hຜtor Moreno²  Ana Grande-Pérez¹  Esteban Domingo² 

[1] Área de Genética, Facultad de Ciencias, Campus de Teatinos, Universidad de Málaga, 29071, Málaga, Spain;Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Campus de Cantoblanco 28049, Madrid, Spain;

关键词: viral quasispecies;    lymphocytic choriomeningitis virus;    5-fluorouracil;    antiviral treatment;   

DOI  :  10.3390/v4112786

来源: mdpi

【 摘 要 】

Lymphocytic choriomeningitis virus (LCMV) has contributed to unveil some of the molecular mechanisms of lethal mutagenesis, or loss of virus infectivity due to increased mutation rates. Here we review these developments, and provide additional evidence that ribavirin displays a dual mutagenic and inhibitory activity on LCMV that can be relevant to treatment designs. Using 5-fluorouracil as mutagenic agent and ribavirin either as inhibitor or mutagen, we document an advantage of a sequential inhibitor-mutagen administration over the corresponding combination treatment to achieve a low LCMV load in cell culture. This advantage is accentuated in the concentration range in which ribavirin acts mainly as an inhibitor, rather than as mutagen. This observation reinforces previous theoretical and experimental studies in supporting a sequential inhibitor-mutagen administration as a possible antiviral design. Given recent progress in the development of new inhibitors of arenavirus replication, our results suggest new options of ribavirin-based anti-arenavirus treatments.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.