Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases

Abstract

Autophagy is an evolutionarily conserved lysosomal degradation system which can recycle multiple cytoplasmic components under both physiological and stressful conditions. Autophagy could be highly selective to deliver different cargoes or substrates, including protein aggregates, pathogenic proteins or superfluous organelles to lysosome using a series of cargo receptor proteins. During viral invasion, cargo receptors selectively target pathogenic components to autolysosome to defense against infection. However, viruses not only evolve different strategies to counteract and escape selective autophagy, but also utilize selective autophagy to restrict antiviral responses to expedite viral replication. Furthermore, several viruses could activate certain forms of selective autophagy, including mitophagy, lipophagy, aggrephagy, and ferritinophagy, for more effective infection and replication. The complicated relationship between selective autophagy and viral infection indicates that selective autophagy may provide potential therapeutic targets for human infectious diseases. In this review, we will summarize the recent progress on the interplay between selective autophagy and host antiviral defense, aiming to arouse the importance of modulating selective autophagy as future therapies toward viral infectious diseases.

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy

“…The host cells employ antiviral selective autophagy, termed viral xenophagy or virophagy, as a defense against invading viruses; components of the autophagy machinery recognize whole virion particles or virion components for clearance [ 8 , 9 ]. On the other hand, viruses have evolved protective mechanisms to evade antiviral autophagy or even to activate certain forms of selective autophagy for successful infection or replication [ 8 , 9 , 10 ]. Of note, selective autophagy of mitochondria, termed mitophagy, is highly activated in human herpesvirus 8 (HHV-8) productive infection and attenuates mitochondria-mediated antiviral responses, including apoptosis and innate immune responses [ 8 ].…”

FAM46C Is an Interferon-Stimulated Gene That Inhibits Lentiviral Particle Production by Modulating Autophagy

“…Autophagy is a complex lysosomal degradation process through which cells maintain their homeostasis by eliminating/recycling intracellular components such as organelles or misfolded proteins. The selected material is targeted for autophagic degradation by a series of specific cargo receptors, among which the most characterized is p62 ( 19 ). The targeted material is then engulfed by a specialized double-membrane vesicle, the autophagosome, which is composed by several accessory proteins, including lipidated LC3 (LC3-II).…”