We found that the viral DUB that is physiologically released from the large tegument protein during productive infection via caspase-1-mediated cleavage [32] selectively protects TOP2α and TOP2β from proteasomal degradation in cells treated with topoisomerase poisons, and is recruited to protein complexes containing TOP2α and TOP2β, effectively counteracting their ubiquitination (Figs 1 and 2A). This evidence concerns the gene ZUP1 and infection.