Quasispecies Theory and the Behavior of RNA Viruses

Abstract

A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy.

Cooperation between different RNA virus genomes produces a new phenotype

“…A n RNA virus population generally evolves rapidly under selection pressure, because of the high error rate of viral RNA polymerase [1][2][3][4][5] . This feature of RNA viruses is thought to have an important role in viral pathogenesis and survival under selection pressure, exemplified in the evolution of the human immunodeficiency virus and the hepatitis C virus 3,[5][6][7] .…”

“…This feature of RNA viruses is thought to have an important role in viral pathogenesis and survival under selection pressure, exemplified in the evolution of the human immunodeficiency virus and the hepatitis C virus 3,[5][6][7] . The high mutation rate may allow these viruses to develop resistance to host immune responses and antiviral drugs, a major complication in the efforts to control their infection.…”

Development and Application of a RT-NestPCR Assay for Differential Detection of C-Strain and Wild-Type Viruses of Classical Swine Fever Virus

“…RNA viruses will generate a diverse mutant repertoire within several generations for they replicate at a high mutation rate and a complex mutant distributions termed as viral quasispecies can be formed (Woo & Reifman, 2012). According to population genetics, the frequency of a given variant in a population is mainly determined by its fitness reflected by its ability of survival and proliferation (Lauring & Andino, 2010). Among the tested vaccines, 7 batches were produced in rabbits and 7 batches were produced by cell culture.…”

The emergence of drug resistant HIV variants and novel anti–retroviral therapy

“…Such prominent inaccuracy of retroviral RT results from a lack of proofreading in combination with a physically large active site [15] . In addition, recombination or the re-arrangement of viral alleles during reverse transcription provides the means for the selection of recombinants with increased fitness [16][17][18] . The wide dispersion of circulating recombinant forms (CRF) demonstrates the impact of viral gene assortment in diversity of HIV variants with increased fitness worldwide [12,19,20] .…”