Here, we demonstrate that: (i) HCMV infection induces IL-1β expression and release, and that this effect is significantly strengthened upon infection with an HCMV pp65 mutant, which is unable to express UL83-encoded pp65 (v65Stop); (ii) NF-κB is a relevant transcription factor that is involved in the IL-1β promoter activation; and finally, (iii) HCMV primes IL-1β expression in a caspase-8 dependent manner. Here, IL1B is linked to cytomegalovirus infection.