Bertram L. Jacobs, Arizona State University, Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Tempe, AZ, 85287, USA. Email: bjacobs@asu.edu
Poxviruses have been long regarded as potent inhibitors of apoptotic cell death. More recently they have been shown to inhibit necroptotic cell death through two distinct strategies. These strategies involve either blocking virus sensing by the host pattern recognition receptor, DAI/ZBP1, or alternatively blocking a later stage in necroptosis by inhibition of activation of the executioner of necroptosis, MLKL. The former, specifically blocks DAI/ZBP1-dependent necroptosis, leaving viruses susceptible to the death-receptor, and potentially TRIF-dependent necroptosis. The latter likely inhibits all modes of necroptotic cell death. As with inhibition of apoptosis, the evolution of potentially redundant viral mechanisms to inhibit programmed necroptotic cell death emphasizes the importance of this pathway in the arms race between hosts and pathogens.