Aleutian mink disease virus (AMDV) enhances viral replication by downregulating JNK protein to promote apoptosis

AMDV induces apoptosis via the mitochondrial pathway without activating extrinsic pathways. • AMDV promotes its replication by downregulating host JNK protein. • JNK acts as a protective factor by mitigating AMDV-induced apoptosis and G1 cell cycle arrest. • Enhancing JNK activity suppresses AMDV production in a dose-dependent manner. • Targeting the JNK pathway offers a novel strategy for controlling AMDV. Aleutian mink disease virus (AMDV) is a pathogen that causes severe illness in minks, leading to substantial economic losses in the mink farming industry. This study investigated the influence of c-Jun N-terminal kinase (JNK), a host cell protein, on the pathological effects of AMDV in infected cells. AMDV infection caused extrinsic apoptotic pathway with Bax translocation, Cytochrome C release, and caspase-9/3 activation. Proteomic and Western blot analyses confirmed that JNK protein was downregulated after infection. JNK mRNA expression was unaffected at 12–48 h post-infection, whereas cycloheximide chase assays（CHX) showed faster JNK protein loss in infected cells. Because MG132 restored JNK levels while chloroquine had no effect, this degradation is proteasome-dependent. Phosphorylation of JNK and c-Jun also decreased during infection. Overexpressing JNK attenuated apoptosis and G1 arrest, reversed p53 and p21 induction, restored CDK4, and suppressed viral titers and genome copynumbers; JNK silencing had the opposite apoptotic effect. Together, these results show that JNK restricts AMDV in F81 cells and that the virus impairs thispathway by accelerating JNK proteasomal degradation.