Herpes simplex virus 1 infection triggers multiple changes in the metabolism of host cells, including a dramatic decrease in the levels of NAD+...The infection-induced drop in NAD+ was dependent on viral DNA replication, presumably due to DNA damage signals produced during this process...We conclude that NAD+ levels drop in HSV-1-infected cells due to the activation of PARP-1/2 and that infection actively modulates the balance between PARP and PARG, presumably to modulate the outcome of PARP activation.