Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants

Since a first version of this article on the relevance of quasispecies to viral disease control was published by one of us [1], an explosion of information on viral quasispecies has been gathered by several groups. For many viruses, extreme complexity at the population level has been documented by direct copying into cDNA of viral RNA extracted from biological specimens using reverse transcriptase and amplification by thermostable polymerases (RT-PCR).Two systems relevant to human health for which extensive population heterogeneity has been revealed are hepatitis C virus (HCV) [2-4] and the human immunodeficiency viruses (HIV) [5-7, and references therein]. Particularly dramatic has been the inability to produce effective vaccines against any of these viruses [8-11] in spite of an urgent need to stop the progression of the AIDS pandemic. Also, the systematic selection of HIV-1 mutants resistant to antiretroviral inhibitors [12-14] has greatly limited the efficacy of antiretroviral treatments until the recent encouraging results with combination therapy.