Viral error catastrophe by mutagenic nucleosides

Annu Rev Microbiol. 2004;58:183-205. doi: 10.1146/annurev.micro.58.030603.123649.

Abstract

Riboviruses and retroviruses have the highest rates of mutations of any known organism. Increasing the mutation rate of these viruses could exceed the error threshold for viability of a viral population within a host. Recent experiments with mutagenic nucleoside analogs validate this new approach to treating infection of RNA viruses. Lethal mutagenesis with HIV-infected cells in culture has been documented and has been postulated to be the mechanism for treatment of hepatitis C with ribavirin. We consider the viral dynamics involved in the formation of a quasispecies, the choice of mutagenic nucleoside analogs, and the studies that have demonstrated the feasibility of lethal mutagenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • HIV / genetics
  • HIV / metabolism
  • HIV Infections / drug therapy
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy
  • Humans
  • Models, Genetic
  • Mutagenesis / genetics*
  • Nucleosides / genetics*
  • Nucleosides / pharmacology
  • RNA Viruses / genetics*
  • Ribavirin / therapeutic use

Substances

  • Antiviral Agents
  • Nucleosides
  • Ribavirin