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Review
. 2013;9(12):e1003760.
doi: 10.1371/journal.ppat.1003760. Epub 2013 Dec 5.

Coronaviruses as DNA wannabes: a new model for the regulation of RNA virus replication fidelity

Everett Clinton Smith  1 , Mark R Denison  2
Affiliations
Review

Coronaviruses as DNA wannabes: a new model for the regulation of RNA virus replication fidelity

Everett Clinton Smith et al. PLoS Pathog. 2013.
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. CoV genomic architecture and nonstructural proteins (nsps).
A. Shown is a linear schematic of the SARS-CoV genome containing both the nonstructural protein (nsp) and the structural and accessory protein open reading frames. The −1 ribosomal frameshift between nsps 10 and 12 is shown by the offset boxes. Boxes denoting each individual nsp are scaled according to amino acid length, and products of polyprotein 1a (nsps1–10) and 1ab (nsps12–16) processing are shown. Colors are as follows: orange (nsp7), green (nsp8), cyan (nsp9), yellow (nsp10), red (nsp12: RNA-dependent RNA polymerase [RdRp]), and blue (nsp14: 3′-to-5′ exoribonuclease [ExoN] and N7-methyltranferase [N7-MTase]). B. A linear schematic of nsp14 is shown. The ExoN domain is colored solid blue, while the N7-MTase domain is hatched blue and white. The zinc-finger domain (ZnF) is shown in gray. DE-D-D residues characteristic of the DEDDh exonuclease superfamily are shown as white boxes. C. A model of how nsps7–8 could assemble on viral dsRNA and interact with the putative multi-subunit CoV polymerase complex consisting of nsps10, 12, and 14. Colors are the same as in panel A, except the two forms of nsp8 (I and II) are shown in green and light green respectively. A short (∼6 n.t.) primer generated by the non-canonical RdRp activity of nsp8 is shown. Binding of ssRNA by nsp9 is also shown.
Figure 2
Figure 2. Loss of ExoN activity dramatically increases the sensitivity of CoVs to RNA mutagens.
The distribution of characteristic 5-fluorouracil (5-FU)-mediated mutations (A-to-G and U-to-C) across the genomes of ExoN+ (wild-type; black) and ExoN− (gray) SARS-CoV following treatment with 0 µM (A) or 400 µM (B) 5-FU during single-cycle replication as determined by Illumnia deep sequencing. Each mutation is denoted as a vertical line, with line height representing the frequency of each mutation within the viral population. The genomic schematic below each panel show the approximate position of each mutation. Data are originally from .
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