Quasispecies Theory and the Behavior of RNA Viruses 英文参考文献.docVIP

Review QuasispeciesTheoryandtheBehaviorofRNAViruses AdamS.Lauring1,RaulAndino2* 1DepartmentofMedicine,UniversityofCalifornia,SanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,2DepartmentofMicrobiologyandImmunology, UniversityofCalifornia,SanFrancisco,SanFrancisco,California,UnitedStatesofAmerica virussequencemaybedeterminedmorebyitsfreedomtomutate into related sequences than by its own replicative capacity. Abstract:Alargenumberofmedicallyimportantviruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. Thisdiversityallowsaviralpopulationtorapidlyadaptto dynamicenvironmentsandevolveresistancetovaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for Second, many viruses operate near a threshold of ‘‘error catastrophe’’andmaybecombatedbyincreasingtheirreplication error rates. Third, increasing the fidelity of genome replication mayparadoxicallyattenuateviruses. Error-ProneReplicationandViralQuasispecies understanding RNA viral evolution. A quasispecies is a Most viruses encode enzymes responsible for replicating their cloud of diverse variants that are genetically linked DNAorRNAgenomes.Theintrinsicerrorrate,orfidelity,ofthe through mutation, interact cooperatively on a functional replicase determines the mutation rate for that virus and the level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory runcountertotraditionalviewsofmicrobialbehaviorand evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its rele- vanceforourunderstandingofviralfitness,virulence,and antiviraltherapeuticstrategy. range of genetic variation upon which natural selection can act. ViralRNApolymerasesexhibitcharacteristicallylowfidelitywith me