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Review
. 2015 May:479-480:46-51.
doi: 10.1016/j.virol.2015.03.022. Epub 2015 Mar 29.

Viral quasispecies

Affiliations
Review

Viral quasispecies

Raul Andino et al. Virology. 2015 May.

Abstract

New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.

Keywords: Adaptation; Evolution; Genome sequencing; Pathogenesis; Quasispecies; Virus.

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Figures

Figure 1
Figure 1
Schematic representation of a transition from a population in which complementation prevails into a population dominated by interference produced by defector genomes whose proportion increases with the mutation rate. See text for references. [The figure is reproduced from (Domingo et al., 2012), with permission from the American Society for Virology, Washington DC, USA].
Figure 2
Figure 2
Illustration of a lethal defection mechanism mediated by a trans-acting protein which is functional as a hexamer. Yellow, blue and red colors represent a gene and encoded protein with increasing numbers of amino acid substitutions. Substituted monomers display interfering potential by virtue of forming chimeric hexamers with reduced activity. [The figure is reproduced from (Domingo et al., 2012), with permission from the American Society for Virology, Washington DC, USA].
Figure 3
Figure 3
(A) Schematic representation of CirSeq procedure. Short viral genomic fragments (~90b) are circularized to serve as templates for rolling-circle cDNA synthesis. The resulting tandem repeats are sequenced as a single read. The repeats can be subsequently identified and aligned. The red symbol represents true genetic variation, which, because are present in the viral genome RNA template, appear in each repeat. The yellow symbols represent sequencing errors. Sequencing errors are unlikely to occur in each of the three repeats, and thus can be identified and excluded from the consensus sequence. (B and C) Fitness values shown on a scale of red (lethal) to white (neutral) to blue (highly beneficial) on poliovirus polymerase and protease. (B) A split view of the active core reveals strong negative selection in regions associated with essential polymerase functions: RNA binding and catalysis. (C) The front view of the poliovirus protease shows the active core where a number of residues are under strong negative selection essential protease functions.

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