Autophagy and Viral Infection

Mao, Jingrong; Lin, Eena; He, Ling; Yu, J.; Tan, Peng; Zhou, Yubin

doi:10.1007/978-981-15-0606-2_5

Cited by 104 publications

(92 citation statements)

References 161 publications

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“…The most apparent hint suggesting a connection between autophagy and the coronavirus replication cycle is the hallmark presence of DMVs in both cases [23,27,28]. Coronavirus induce characteristic rearrangements of the ER membranes towards the generation of connected DMVs and convoluted membranes.…”

Section: Both Autophagy and Coronavirus Induce The Formation Of Analomentioning

confidence: 98%

“…Among other types of selective autophagy, xenophagy specifically targets intracellular pathogens for their degradation and further integration into both innate and adaptive immune responses [21,[23][24][25][26]. Conversely, in response to this cell-protective autophagy, several different families of viruses, including coronavirus, have adapted by evolving a large variety of strategies to escape and/or to benefit via the inhibition and/or stimulation of autophagy at different stages of the process [23,[27][28][29]. Thus, the identification of these interaction points might bring the opportunity to disrupt the viral replication cycle at specific stages by targeting selected steps of autophagy.…”

Section: Autophagy Interplays With the Replication Cycles Of Multiplementioning

confidence: 99%

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Canonical and Noncanonical Autophagy as Potential Targets for COVID-19

Belló-Pérez

Sola

Novoa

et al. 2020

Cells

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The SARS-CoV-2 pandemic necessitates a review of the molecular mechanisms underlying cellular infection by coronaviruses, in order to identify potential therapeutic targets against the associated new disease (COVID-19). Previous studies on its counterparts prove a complex and concomitant interaction between coronaviruses and autophagy. The precise manipulation of this pathway allows these viruses to exploit the autophagy molecular machinery while avoiding its protective apoptotic drift and cellular innate immune responses. In turn, the maneuverability margins of such hijacking appear to be so narrow that the modulation of the autophagy, regardless of whether using inducers or inhibitors (many of which are FDA-approved for the treatment of other diseases), is usually detrimental to viral replication, including SARS-CoV-2. Recent discoveries indicate that these interactions stretch into the still poorly explored noncanonical autophagy pathway, which might play a substantial role in coronavirus replication. Still, some potential therapeutic targets within this pathway, such as RAB9 and its interacting proteins, look promising considering current knowledge. Thus, the combinatory treatment of COVID-19 with drugs affecting both canonical and noncanonical autophagy pathways may be a turning point in the fight against this and other viral infections, which may also imply beneficial prospects of long-term protection.

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Section: Both Autophagy and Coronavirus Induce The Formation Of Analomentioning

confidence: 98%

Section: Autophagy Interplays With the Replication Cycles Of Multiplementioning

confidence: 99%

Canonical and Noncanonical Autophagy as Potential Targets for COVID-19

Belló-Pérez

Sola

Novoa

et al. 2020

Cells

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“…(294,295) By packaging viral particles for lysosomal degradation and antigen-presentation, autophagic encapsulation provides an initial step in development of adaptive antiviral immune responses. (296) However, it is important to recognize that some viruses are able to hijack components of autophagy to promote viral replication. For example, hepatitis C virus infection is known to promote autophagy, (297) but the resulting lipidfilled autophagosomes can act to enhance the assembly of hepatitis C virions.…”

Section: Vitamin D and Antiviral Innate Immunitymentioning

confidence: 99%

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

et al. 2020

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Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic Tregulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function.

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“…Autophagy maintains cellular organelle homeostasis by clearing cellular waste and providing the cell with a supply of energy when nutrients are scarce (18). Autophagy also functions as the first line of defense to cleanse the cell of invading pathogens such as viruses, and plays an important role in mediating the innate immune response (19).…”

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators

Gorshkov

Chen

Bostwick

et al. 2020

Preprint

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One Sentence Summary: Blocking SARS-CoV-2 cytopathic effects with selective autophagy inhibitors underlying the clinical benefits of chloroquine and hydroxychloroquine. Abstract:SARS-CoV-2 is a new type of coronavirus capable of rapid transmission and causing severe clinical symptoms; much of which has unknown biological etiology. It has prompted researchers to rapidly mobilize their efforts towards identifying and developing anti-viral therapeutics and vaccines. Discovering and understanding the virus' pathways of infection, host-protein interactions, and cytopathic effects will greatly aid in the design of new therapeutics to treat COVID-19. While it is known that chloroquine and hydroxychloroquine, extensively explored as clinical agents for COVID-19, have multiple cellular effects including inhibiting autophagy, there are also dose-limiting toxicities in patients that make clearly establishing their potential mechanisms-of-action problematic. Therefore, we evaluated a range of other autophagy modulators to identify an alternative autophagy-based drug repurposing opportunity. In this work, we found that 6 of these compounds blocked the cytopathic effect of SARS-CoV-2 in Vero-E6 cells with EC50 values ranging from 2.0 to 13 µM and selectivity indices ranging from 1.5 to >10-fold. Immunofluorescence staining for LC3B and LysoTracker dye staining assays in several cell lines indicated their potency and efficacy for inhibiting autophagy correlated with the measurements in the SARS-CoV-2 cytopathic effect assay. Our data suggest that autophagy pathways could be targeted to combat SARS-CoV-2 infections and become an important component of drug combination therapies to improve the treatment outcomes for COVID-19.

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Autophagy and Viral Infection

Cited by 104 publications

References 161 publications

Canonical and Noncanonical Autophagy as Potential Targets for COVID-19

Canonical and Noncanonical Autophagy as Potential Targets for COVID-19

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

The SARS-CoV-2 cytopathic effect is blocked with autophagy modulators

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