Viruses and autophagy

Abstract

SUMMARY Autophagy is an evolutionarily conserved intracellular process by which bulk cytoplasm is enveloped inside a double-membraned vesicle and shuttled to lysosomes for degradation. Within the last 15 years, the genes necessary for the execution of autophagy have been identified and the number of tools for studying this process has grown. Autophagy is essential for tissue homeostasis and development and defective autophagy is associated with a number of diseases. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy and/or autophagy genes likely play both anti-viral and proviral roles in the life cycles and pathogenesis of many different virus families. With respect to anti-viral roles, the autophagy proteins function in targeting viral components or virions for lysosomal degradation in a process termed xenophagy, and they also play a role in the initiation of innate and adaptive immune system responses to viral infections. Consistent with this anti-viral role of host autophagy, some viruses encode virulence factors that interact with the host autophagy machinery and block the execution of autophagy. In contrast, other viruses appear to utilise components of the autophagic machinery to foster their own intracellular growth or non-lytic cellular egress. As the details of the role(s) of autophagy in viral pathogenesis become clearer, new anti-viral therapies could be developed to inhibit the beneficial and enhance the destructive aspects of autophagy on the viral life cycle.

Hepatocellular carcinoma and the risk of occupational exposure

“…Initially, autophagy functions are as a tumor suppressor and later, when HCC has developed, the autophagy may contribute to its growth [303,305] . Microbes have evolved mechanisms to evade and exploit autophagy and both HBV and HCV use autophagy for their own survival [306] . Studies have shown that autophagy enhances viral replication at most steps of HBV replication and that autophagy proteins are likely to be factors for the initial steps of HCV replication [307,308] .…”

Cell death in the pathogenesis and progression of heart failure

“…Selective forms of autophagy mediate degradation of specific damaged organelles: mitochondria (mitophagy), ER (ER-phagy), peroxysomes (pexophagy), ribosomes (ribophagy) and intracellular pathogens (xenophagy) [26][27][28][29][30]. Given the paramount multifacetal roles of mitochondria, selective autophagic removal of dysfunctional mitochondria, mitophagy, is attracting increasing interest.…”

Autophagy Modulation As a Potential Therapeutic Target for Liver Diseases

“…However, the microbes have also evolved mechanism to evade and exploit autophagy and both HBV and HCV have adapted to use autophagy for their own survival. 66 HCV utilizes various autophagy components for its own replication. 67 Studies have shown that there is an accumulation of autophagic vacuoles in HCV-infected hepatocytes; however this autophagy is inefficient as the autophagosomes are not able to increase autophagic protein degradation.…”