Schematic overview of the relationships between autophagy (or autophagy proteins) and viral infection. Adaptive immunity (purple shaded region): Autophagy delivers endogenously synthesized viral proteins to MHC class II-loading compartments (MIIC), where they are loaded onto MHC class II molecules for presentation to CD4⁺ T cells. Cooperation with innate immunity (blue shaded region): After virus infection, dsRNA structures activate the interferon-inducible antiviral molecule, PKR, which induces autophagy. Virions are engulfed in autophagosomes and degraded within the autolysosome. The HSV-1 virulence protein, ICP34.5, antagonizes both PKR activity and the autophagy protein Beclin 1 while viral Bcl-2 family members antagonize Beclin 1 to suppress autophagy induction. Viral nucleic acids are delivered by autophagosomes to endosomes containing toll like receptor (TLR7), which induces type 1 interferon (IFN) production. Suppression of innate immunity (pink shaded region): Recognition of viral nucleotides through TLR3, 7 and 9 may induce NLRP3 activation, which mediates caspase-1 activation. Active caspase-1 processes an IL-1β precursor into a mature cytokine, which is secreted. Atg16l1 blocks this process and Atg16l1 deletion results in increased IL-1β secretion. The Atg5–Atg12 conjugate suppresses the type I IFN response via retinoic acid-inducible gene I (RIG-I) and IFN-β promoter stimulator-1 (IPS-I) inhibition. Utilization of autophagy machinery (green shaded region): Poliovirus infection induces double-membraned vesicles that contain autophagy marker proteins. Viral RNA synthesis occurs in association with these membrane vesicles, but autophagy proteins are not essential for poliovirus replication. Poliovirus may also utilize autophagosome-like structures to exit from the cell without lysis, via fusion of the double-membraned vesicle with the plasma membrane. Hepatitis C virus (HCV) induces double-membraned vesicles that contain autophagy markers through activation of the unfolded protein response (UPR) and blocks autophagosomal maturation. The double-membraned vesicles do not co-localize with HCV proteins, suggesting that HCV is neither targeted for autophagosomal degradation, nor uses autophagosome-like structures for viral replication or morphogenesis. Autophagy proteins are, however, required for enhanced HCV replication through mechanisms that are not yet defined. Throughout figure, dotted lines represent cross-talk that is either speculative or occurs by unknown, and possibly, indirect mechanisms. See text for further details.