African swine fever virus MGF_110-8L promotes host cell autophagy and suppresses interferon signaling by activating the unfolded protein response.

African swine fever virus (ASFV) infection induces cellular stress that activates the unfolded protein response (UPR), a key pathway for restoring endoplasmic reticulum (ER) homeostasis. However, the mechanisms by which ASFV modulates the UPR remain incompletely understood. Here, we identify the ASFV protein MGF_110-8L as a key regulator of the UPR, leading to the dissociation and activation of the UPR sensors PERK, IRE1α, and ATF6, which subsequently restore ER homeostasis. Moreover, MGF_110-8L triggers UPR-dependent autophagy, which in turn contributes to the suppression of type I interferon-mediated immune responses. Deletion of MGF_110-8L (ASFV-Δ8 L) markedly reduced the activation of both UPR and autophagy pathways and led to enhanced type I interferon responses. Together, our findings reveal a novel mechanism by which an ASFV protein activates the host UPR-autophagy axis to restore cellular homeostasis and modulate host innate immunity, highlighting MGF_110-8L as a potential target for therapeutic development.