Autophagy gene-dependent intracellular immunity triggered by interferon-γ.

Interferon-γ (IFNγ) is a critical mediator of cell-intrinsic immunity to intracellular pathogens. Understanding the complex cellular mechanisms supporting robust interferon-γ-induced host defenses could aid in developing new therapeutics to treat infections. Here, we examined the impact of autophagy genes in the interferon-γ-induced host response. We demonstrate that genes within the autophagy pathway including , , and , as well as ubiquitin ligase complex genes and are required for IFNγ-induced inhibition of murine norovirus (norovirus hereinafter) replication in mouse cells. and were also required for IFNγ-mediated restriction of parasite growth within the parasitophorous vacuole in human cells. Furthermore, we found that perturbation of UFMylation pathway components led to more robust IFNγ-induced inhibition of norovirus via regulation of endoplasmic reticulum (ER) stress. Enhancing or inhibiting these dynamic cellular components could serve as a strategy to control intracellular pathogens and maintain an effective immune response.