ATM and ATR inhibit Ad replication whereas E4orf4 enhances it.

<p>(<b>A</b>) ATM-deficient A-T cells, reconstituted with WT ATM or with an empty vector, were infected with the Ad mutants <i>dl366*</i> and <i>dl366*+E4orf4</i> (30 ffu/cell), or were mock infected. An ATR inhibitor (ATRi) was added to parallel cell samples as described in the methods section. The cells were visualized 24 hrs post infection using a Zeiss Axioskop at a magnification of 100. Representative pictures of two independent experiments are shown. The percent of area covered with cells out of the total field area (ce) was determined using Image-Pro Premier 9.1 and the percent of area covered with cell clusters larger than 6000 pixels<sup>2</sup> out of total cell area (cl), was calculated using FIJI. (B) Viruses from two independent experiments performed as described in A were collected from infected cells 24 hrs post infection and their titer was determined. Data is displayed in box plots as previously described [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005420#ppat.1005420.ref072" target="_blank">72</a>] and black dots represent outliers. Statistical significance was calculated using unpaired t-test and p values of significant differences between <i>dl366*</i> and <i>dl366*+E4orf4</i> viruses are shown.</p>