Autophagy and antiviral immunity

Abstract

Autophagy is an ancient pathway designed to maintain cellular homeostasis by degrading long-lived proteins and organelles in the cytosol. Recent studies demonstrate that autophagy is utilized by the cells of the innate and adaptive immune systems to combat viral infections. Autophagy plays a key role in recognizing signatures of viral infection, and represents a critical effector mechanism to restrict viral replication. On the other hand, autophagosomes have been exploited by certain viruses as a niche for viral replication. Furthermore, autophagy can be used to deliver endogenous viral antigens to the MHC class II loading compartment, allowing activation of CD4 T cells. In this review, we describe recent advances in the field of autophagy as it relates to innate and adaptive antiviral immune responses.

Figure 1

The role of autophagy in antiviral immune responses. An example of viral subversion, degradation and innate recognition is depicted. Viral subversion: The positive strand RNA of poliovirus is translated by ribosomes and viral proteins are synthesized. Some of these proteins (2BC and 3A) trigger the induction of double membrane vesicle from endoplasmic reticulum (ER) by exploiting cellular machinery for autophagy. Viral RNA synthesis occurs in the vicinity of these membrane vesicles. Newly formed virus is released from the cell by lysis or possibly by fusion of autophagosomal membrane with plasma membrane. Viral degradation: After HSV-1 infection, dsRNA structures activate PKR, which in turn induces autophagy. HSV-1 virions are engulfed in autophagosomal structures and are degraded within the autolysosome. ICP34.5, a virulence protein encoded by HSV-1, antagonizes PKR function to suppress the induction of autophagy. Innate recognition: In pDCs, cytosolic RNA replication intermediates of VSV infection are engulfed by autophagosome and are delivered to the lysosome upon fusion. TLR7 is activated in the lysosome by recognition of such replication intermediates and triggers the induction of antiviral genes such as IFN-α and IL-12.