Model for genetic conflict involving PARP macrodomains.

<p>(A) Model for macro-PARP function. ADP-ribosylated host or viral proteins may be a signal for recruitment of PARP9, 14 or 15, which could facilitate additional recruitment of antiviral effectors, and amplify the initial ADPr signal. (B–D) Three models for how viruses may antagonize macro-PARP function. Viruses lacking their own macrodomains may use other proteins to directly antagonize macro-PARP proteins (B), driving recurrent positive selection in macro-PARP genes to escape antagonism. Macrodomains encoded by viruses (e.g. corona- and togaviruses) may catalyze the removal of ADPr (C) or compete with macro-PARPs for binding to ADPr (D) in order to antagonize host ADPr-mediated signaling.