The IFI16-H2B complex is mainly involved in inflammasome independent STING-mediated IFN-β production as shown by the association of cytoplasmic IFI16-H2B-BRCA1 complex with cGAS and STING to form a signal hub and IFN-β production (Fig 10C), absence of IFI16-STING association in H2B knockdown cells during KSHV de novo infection (Fig 6G), absence of H2B interaction with ASC (Fig 2B and 2D) and absence of STING interaction with ASC (S6C–S6E Fig). Here, IFNB1 is linked to infection.