Regulation of Innate Immune Responses by Autophagy: A Goldmine for Viruses

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.

Mechanics of a molecular mousetrap—nucleation-limited innate immune signaling

“…Complete elimination of the self-templating polymers is required for the cell to ''reset'' by again accumulating the proteins to supersaturating levels. Wholesale destruction of the polymers by autophagy appears to be a general way to accomplish this, as has been shown for the Bcl10, MAVS, MyD88, and ASC signalosomes (74,75). Any transient change in cytosolic pH or other control knobs of signalosome protein affinities could also allow for total dissolution of the polymers.…”

Comparative Transcriptome Analysis Reveals the Molecular Immunopathogenesis of Chinese Soft-Shelled Turtle (Trionyx sinensis) Infected with Aeromonas hydrophila

“…Serious infectious diseases caused by pathogens including bacteria and viruses is threatening the aquaculture of turtles [ 3 ]; in particular, the hemorrhagic sepsis caused by A. hydrophila , with more than 15 kinds of diseases, is the most common and troublesome in turtle disease cases [ 36 , 37 ]. Previous studies have reported in mammals and fish that abnormal immune responses to pathogenic infections, such as excessive activation of immune cells and dysfunction of immune responses, can lead the immune system to attack self-uninfected cells, causing systemic inflammation, tissue hemorrhagic sepsis, and even death [ 38 , 39 ]. However, the research on the immune response mechanisms is limited, and the molecular pathology of turtles infected by A. hydrophila remains unclear, which greatly hinders the strategy innovations for disease prevention and control in Chinese soft-shelled turtles.…”

Coronavirus Usurps the Autophagy-Lysosome Pathway and Induces Membranes Rearrangement for Infection and Pathogenesis

“…SARS-CoV-2 NSP4 and NSP6 induce ER-derived DMVs independent of the autophagic pathway by hijacking the host cell ERAD machinery ( Muscolino et al, 2020 ). In addition, prior studies indicate that SARS-CoV NSP2 and MERS-CoV NSP3 could induce extensive rearrangement of cellular autophagosome-like vesicles around the ER and the Golgi apparatus ( Pradel et al, 2020 ). The majority of host cells undergo ER stress after CoV infection.…”

“…The NSP3 PLP-TM domain is necessary to complex Beclin1 to STING1, which prevents the stimulation of IFN production ( Zhang et al, 2021 ). In the absence of IFNs, it is difficult for host cells to eliminate the virus through innate immunity ( Pradel et al, 2020 ).…”