SAAL1 negatively regulates antiviral innate immunity by suppressing MAVS aggregation

The mitochondrial antiviral signaling protein (MAVS) is a crucial adaptor for the innate immune receptor retinoic acid inducible gene 1 in recognizing viral RNA. Upon viral infection, MAVS undergoes lysine 63 (K63)-linked polyubiquitination, mediated by tripartite motif-containing 31 (TRIM31) and subsequently forms prion-like aggregates to activate downstream signaling cascades, ultimately leading to the production of type I interferons (IFNs). We identified serum amyloid A-like 1 (SAAL1) as a negative regulator of MAVS. SAAL1 antagonizes the K63-linked polyubiquitination and aggregation of MAVS by impeding TRIM31 for association with MAVS. Mechanistically, SAAL1 is dephosphorylated at threonine 387 and translocated to cytosol upon SeV infection, subsequently exerting a negative regulatory effect on type I IFN signaling. These findings establish SAAL1 as a modulator of MAVS and uncover mechanisms through which SAAL1 regulates antiviral innate immunity.