Comparison of viral mutation rates and effect of A3-mediated editing.

<p><b>A.</b> Mutation rates per base per cell are shown for HIV-1, bacteriophage Qβ, HCV, poliovirus, human rhinovirus 14, vesicular stomatitis virus (VSV), influenza A virus, tobacco etch virus (TEV), tobacco mosaic virus (TMV), murine hepatitis virus (MHV), influenza B virus, bacteriohages ϕ6, ϕX174, m13, λ and T2, and herpes simplex virus 1 (HSV). RNA viruses are shown in red and DNA viruses in blue. Two HIV-1 data points are shown in pink, one obtained from cell culture studies [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002251#pbio.1002251.ref004" target="_blank">4</a>] (which is similar to the estimate obtained here using plasma RNA), and the estimate obtained here from PBMC DNA. All other mutation rates were taken from a review [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002251#pbio.1002251.ref004" target="_blank">4</a>] except for Qβ [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002251#pbio.1002251.ref063" target="_blank">63</a>]. Numerical values can be retrieved from these references. Other reverse-transcribing viruses are believed to exhibit mutation rates similar to those of RNA viruses, but these are not shown because previous work did not address the potentially strong contribution of A3 in vivo. Notice that the mutation rate axis is in log-scale, such that the HIV-1 mutation rate is 37 times higher than the second highest rate, and also substantially higher than the rate obtained from plasma RNA or under cell culture conditions. <b>B.</b> According to our interpretation, this discrepancy occurs because most A3-edited sequences are lethally mutated and are thus unable to reach the plasma. Therefore, analysis of plasma RNA sequences would lead to a gross underestimation of the actual HIV-1 mutation rate.