Digesting Oneself and Digesting Microbes: Autophagy as a Host Response to Viral Infection

Although research in this area is still in a stage of infancy, it seems likely that the lysosomal degradation pathway of autophagy plays an evolutionarily conserved role in antiviral immunity. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. Given this role of autophagy in innate immunity, it is not surprising that viruses have evolved numerous strategies to inhibit host autophagy. Different viral gene products can either modulate autophagy regulatory signals or directly interact with components of the autophagy execution machinery. Moreover, certain RNA viruses have managed to “co-apt” the autophagy pathway, selectively utilizing certain components of the dynamic membrane rearrangement system to promote their own replication inside the host cytoplasm. In addition to this newly emerging role of autophagy in innate immunity, autophagy plays an important role in many other fundamental biological processes, including tissue homeostasis, differentiation and development, cell growth control, and the prevention of aging. Accordingly, the inhibition of host autophagy by viral gene products has important implications not only for understanding mechanisms of immune evasion, but also for understanding novel mechanisms of viral pathogenesis. It will be interesting to dissect the role of viral inhibition of autophagy in acute, persistent, and latent viral replication, as well as in the pathogenesis of cancer and other medical diseases.