Schematic model depicting herpesvirus infection induced IFI16 acetylation and its role in inflammasome and IFN-β production.

<p>Results presented here demonstrate viral DNA entry into the nucleus (1–2) leads to recognition through IFI16 (3) followed by IFI16 acetylation (4). The acetylated IFI16 forms an inflammasome complex (5) which is translocated to the cytoplasm via RanGTP. Leptomycin B treatment abrogates the acetylated IFI16 translocation (6). The inflammasome complex formation leads into the activation of caspase-1 (7) which in turn cleaves pro-IL-1β and-IL-33 (8), and IL-β is released into the culture supernatant (9). IFI16 acetylation (i) and cytoplasmic redistribution (ii) also activates STING (iii) which phosphorylates IRF-3 (iv) that moves to the nucleus leading into IFN-β gene transcription (v-vi), translation (vii) and IFN-β is secreted into the culture supernatant (viii). Use of p300 inhibitor C-646 and knockdown of p300 does not inhibit the ability of IFI16 to recognize the episomal viral DNA but blocks the acetylation of IFI16 which results in the inhibition of inflammasome formation, IFI16 translocation into the cytoplasm as well as IL-1β and IFN-β production.