Although, the nature of first signal (required for pro-IL-1β and NLRP3 gene expression) during influenza A virus infection is still unknown, there is evidence for the existence of “first signal” during influenza A virus infection, since in vivo (in mice) and in vitro infection with influenza A virus resulted in induction of both pro-IL-1β and NLRP3 gene expression [31]. This evidence concerns the gene IL1B and infection.