Autophagic degradation of MAVS-B by Carassius auratus herpesvirus (CaHV) ORF56 suppresses interferon response in polyploid gibel carp.

Abstract

Targeting key antiviral proteins of the host immune system is a common viral strategy. However, little is known about whether viruses employ more refined immune evasion tactics in the few polyploid animal hosts that exist. Here, we report that ORF56 of Carassius auratus herpesvirus (CaHV) diminishes IFN production by degrading MAVS-B, but not MAVS-A, via the autophagy pathway in amphitriploid (AAABBB) gibel carp (Carassius gibelio) with two triploid sets of chromosomes. Screening assays demonstrated that ORF56 suppresses IFN promoter activity and promotes CaHV replication. ORF56 specifically binds to and degrades gibel carp MAVS-B, a process that can be rescued by autophagy inhibitors. Moreover, co-expression of ORF56 and MAVS-B induces pronounced autophagic flux. Interestingly, although the selective autophagy receptors OPTN-A and OPTN-B both interact with ORF56, only OPTN-B is involved in ORF56 mediated degradation of MAVS-B. In summary, during CaHV infection of polyploid gibel carp, the viral protein ORF56 does not indiscriminately target both MAVS isoforms but selectively degrades MAVS-B through the autophagy pathway. These findings reveal a sophisticated viral immune evasion mechanism adapted for polyploid hosts.