TRIM26 facilitates PRV infection through NDP52-mediated MAVS autophagic degradation

Abstract

Abstract Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses to benefit virus replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26) belonging to TRIM family proteins is engaged in a broad range of biological processes involved in innate immunity, especially in regulating virus infection. Herein, we found that the expression of TRIM26 was significantly induced after PRV infection. Surprisingly, the overexpression of TRIM26 promoted PRV production, while the depletion of this protein inhibited the virus replication, suggesting TRIM26 could positively regulate PRV infection. Further analysis revealed that TRIM26 negatively regulates innate immune response by targeting RIG-I triggered type I interferon signaling pathway. TRIM26 was physically associated with MAVS independent of viral infection and reduced MAVS expression. Mechanistically, we found NDP52 interacted with both TRIM26 and MAVS, and TRIM26-induced MAVS degradation was almost entirely blocked in NDP52 knockdown cells, demonstrating that TRIM26 degrades MAVS through NDP52-mediated selective autophagy. Our results reveal a novel mechanism by which PRV escapes host antiviral innate immunity and enriches insights into the crosstalk among virus infection, autophagy, and innate immune response.