Viral error catastrophe by mutagenic nucleosides.
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.
The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, Washington 98195, USA. jonand@u.washington.edu
Jon P
JP
Anderson
Richard
R
Daifuku
Lawrence A
LA
Loeb
D000998:Antiviral Agents / Q000494:pharmacology; D006678:HIV / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D008957:Models, Genetic; D016296:Mutagenesis / Q000235:genetics*; D009705:Nucleosides / Q000235:genetics* / Q000494:pharmacology; D012328:RNA Viruses / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use
D000998:Antiviral Agents; D009705:Nucleosides; D012254:Ribavirin