Autophagic cell death in viral infection: Do TAM receptors play a role?

Abstract

Containment and clearance of invading pathogens, such as viruses, by suppression of viral replication through antiviral mechanisms (e.g. CRISPR, interferon response or programmed cell death) provide examples of evolutionary developed responses by hosts to limit the establishment of infection. Degradation of the cytoplasm en masse provides an ideal cellular response against intruding pathogens. Degradation of such scale is achieved by a process called (macro)autophagy, where double membrane vacuoles, autophagosomes, engulf cytoplasm and organelles for lysosomal degradation. However, chronic and unrestrained autophagy poses catastrophic consequences to a cell especially when vital organelles (e.g. mitochondria or nucleus) are engulfed and destroyed. Recent findings in the field of autophagy and cell death regulation describe mechanisms that distinguish whether autophagy takes a moderate or excess route. This review aims to present new perspectives and re-examines current assumptions related to cell death regulation by autophagy. The emerging role of TAM receptors in the modulation of autophagy (i.e. both homeostatic and lethal) in the context of virus infections is also discussed in addition to chemical strategies for studying autophagy.