Recent studies from several laboratories, including ours, have established the PYHIN proteins AIM2 and IFI16 as sensors of viral dsDNA, important for eliciting immune and inflammatory responses to infection (Fernandes-Alnemri et al, 2009; Hornung et al, 2009; Rathinam et al, 2010; Unterholzner et al, 2010; Kerur et al, 2011; Li et al, 2012, 2013; Orzalli et al, 2012). Here, IFI16 is linked to infection.