Abstract
Autophagy is a lysosomal degradation pathway for intracellular components and is highly conserved across eukaryotes. This process is a key player in innate immunity and its activation has anti-microbial effects by directly targeting pathogens and also by regulating innate immune responses. Autophagy dysfunction is often associated with inflammatory diseases. Many studies have shown that it can also play a role in the control of innate immunity by preventing exacerbated inflammation and its harmful effects toward the host. The arms race between hosts and pathogens has led some viruses to evolve strategies that enable them to benefit from autophagy, either by directly hijacking the autophagy pathway for their life cycle, or by using its regulatory functions in innate immunity. The control of viral replication and spread involves the production of anti-viral cytokines. Controlling the signals that lead to production of these cytokines is a perfect way for viruses to escape from innate immune responses and establish successful infection. Published reports related to this last viral strategy have extensively grown in recent years. In this review we describe several links between autophagy and regulation of innate immune responses and we provide an overview of how viruses exploit these links for their own benefit.
Highlights
Cellular catabolism is ensured by both the Ubiquitin Proteasome System and the process of autophagy acting in a coordinated manner in order to maintain homeostasis [1]
RUBICON binds to Interferon Regulatory Factor 3 (IRF3) which leads to decreased production of type I IFN The BPLF1 viral protein induces the formation of TRIM25 aggregates which are degraded by p62/SQSTM1, decreasing activation of IRF3 The UL50 viral protein triggers IFNAR lysosomal degradation IFNAR is degraded by autophagy Autophagic degradation of RNA-silencing pathway components: Supressor of Gene Silencing 3 (SGS3) and RNA-Dependent RNA polymerase 6 (RDR6) The NSvc4 viral protein triggers remorin lysosomal degradation Nuclear Dot Protein 52 (NDP52) targets ubiquitinated IRF3
A constant selective pressure is imposed on viruses by their hosts, leading pathogens to adapt in order to replicate efficiently
Summary
Cellular catabolism is ensured by both the Ubiquitin Proteasome System and the process of autophagy acting in a coordinated manner in order to maintain homeostasis [1].
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