Mono-ADP-ribosylation by ARTD10 restricts Chikungunya virus replication by interfering with the proteolytic activity of nsP2

Sarah Krieg; Fabian Pott; Laura Eckei; Maud Verheirstraeten; Mareike Bütepage; Barbara Lippok; Christine Goffinet; Bernhard Lüscher; Patricia Verheugd

To expand on these findings, we determined the effects of ARTD10 and ARTD12 on the 173 replication cycle of infectious CHIKV, which expresses EGFP from an additional subgenomic 174 promoter ( Fig. 1g) [47]. Overexpression of ARTD10 and ARTD12 resulted in a significant 175 decrease of EGFP expressing cells as measured by flow cytometry 24 and 48 hpi ( Fig. 1g and 176 Supplementary Fig. 2 ). In this set-up, the catalytically inactive mutant of ARTD12 restricted 177 replication to the same extend as the wt protein, indicating that ARTD12 may have more than 178 one mode of action. In contrast, ARTD10-GW enhanced viral replication, hinting at a dominant 179 negative effect and thereby demonstrating dependency on catalytic activity of ARTD10 as a 180 CHIKV restriction factor. Of note is also that the inhibitory effects of ARTD10 and ARTD12 are 181 more pronounced at early time points (24 hpi) compared to later time points (48 hpi To gain insight into a possible mechanism of how MARylation by ARTD10 and ARTD12 might 187