RNA毒变异与消失.docVIP

Virus Research 107 (2005) 129–139 Quasispecies dynamics and RNA virus extinction Esteban Domingoa,b,c,? , Cristina Escarm′sa , Ester L′ zarob , Susanna C. Manrubiab?a a Centro de Biolog′a Molecular “Severo Ochoa” (CSIC-UAM), Consejo Superior de Investigaciones Cienti?cas,? Universidad Aut′ noma de Madrid, Cantoblanco, 28049 Madrid, Spaino b Centro de Astrobiolog′a (CSIC-INTA), Carretera de Ajalvir, km 4, 28850 Torrej′ n de Ardoz, Madrid, Spain?o c Centro de Investigaci′ n en Sanidad Animal (INIA), Valdeolmos, 28130 Madrid, Spaino Available online 8 December 2004 Abstract The extinction of foot-and-mouth disease virus (FMDV) is strongly in?uenced by mutation rates, types of mutations, relative viral ?tness and virus population regimens during infection. Here we review experimental results and theoretical models that describe a contrast between the effective extinction of FMDV subjected to increased mutagenesis, and the remarkable resistance to extinction of the same and related FMDV clones subjected to serial bottleneck events. The results suggest procedures to master key parameters to develop effective antiviral strategies based on virus entry into error catastrophe. ? 2004 Elsevier B.V. All rights reserved. Keywords: Foot-and-mouth disease virus; 5-Fluorouracil; 5-Azacytidine; Mutation 1. Introduction Critical for a therapeutic application of error catastrophe as an antiviral strategy is to understand the main factors (in- trinsic to the virus as well as those related to population dy- namics) that may contribute to loss of infectivity. This has proven a complex issue and the experiments carried out so far have raised more questions than provided answers. Here we review studies carried out over the last decade with the impor- tant animal pathogen foot-and-mouth disease virus (FMDV) aimed at understanding how high mutation rates and qua- sispecies dynamics (as opposed to low mutation rates and a non-quasispecies dynamics) affected