The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions

Ke, Po‐Yuan

doi:10.3390/ijms19123940

Cited by 48 publications

(46 citation statements)

References 520 publications

(783 reference statements)

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“…One is to be involved in the assembly and release of the virus by its membrane trafficking character. The other is to adjust the host antiviral immune response [48]. In this study, we found that autophagy inhibition with knockdown of Beclin 1 and LC3B increased the mRNA levels of Type I interferons and IL-6 ( Figure 5A) and also enhanced IRF7 and NF-κB promoter activation ( Figure 5B).…”

Section: Discussionmentioning

confidence: 58%

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Pan

Cheng

et al. 2020

Vaccines

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Duck Tembusu virus (DTMUV) has recently appeared in ducks in China and the key cellular determiners for DTMUV replication in host cells remain unknown. Autophagy is an evolutionarily conserved cellular process that has been reported to facilitate flavivirus replication. In this study, we utilized primary duck embryo fibroblast (DEF) as the cell model and found that DTMUV infection triggered LC3-II increase and polyubiquitin-binding protein sequestosome 1 (p62) decrease, confirming that complete autophagy occurred in DEF cells. The induction of autophagy by pharmacological treatment increased DTMUV replication in DEF cells, whereas the inhibition of autophagy with pharmacological treatments or RNA interference decreased DTMUV replication. Inhibiting autophagy enhanced the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 7 (IRF7) pathways and increased the p62 protein level in DTMUV-infected cells. We further found that the overexpression of p62 decreased DTMUV replication and inhibited the activation of the NF-κB and IRF7 pathways, and changes in the NF-κB and IRF7 pathways were consistent with the level of phosphorylated TANK-binding kinase 1 (p-TBK1). Opposite results were found in p62 knockdown cells. In summary, we found that autophagy-mediated p62 degradation acted as a new strategy for DTMUV to evade host innate immunity.

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Section: Discussionmentioning

confidence: 58%

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Pan

Cheng

et al. 2020

Vaccines

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“…Multiple evidence has indicated that autophagy plays an important role in flavivirus infection (Ke, 2018). But there are rare reports on the effect of autophagy on virus replication in vivo.…”

Section: Introductionmentioning

confidence: 99%

Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Pan

Cheng

et al. 2020

Front. Cell. Infect. Microbiol.

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Duck tembusu virus (DTMUV) is newly emerged in poultry and causes great losses to the breeding industry in China and neighboring countries. Effective antiviral strategies are still being studied. Autophagy is a cellular degradative pathway, and our lab's previous data show that autophagy promotes DTMUV replication in vitro. To study the role of autophagy further in vivo, we utilized ducks as the animal model to investigate the autophagy responses in DTMUV-targeted tissues. And also, we utilized autophagy regulators, including Rapamycin (Rapa) as the autophagy enhancer, 3-Methyladenine (3-MA) and Chloroquine (CQ) as the autophagy inhibitors, to adjust the host autophagic levels and then study the effects of autophagy on tissue damages and virus replication. As a result, we first found DTMUV infection trigged autophagy and autophagy regulator treatments regulated autophagy levels successfully in duck spleens and brains. Next, we found that autophagy inhibitors inhibited DTMUV replication and alleviated DTMUV-induced pathological symptoms, whereas the autophagy inducer treatment led to the opposite effects. And we also found that autophagic regulation was correlated with the expression of innate immune genes, including pattern recognition receptors, type I interferons, and cytokines, and caused different effects in different tissues. In summary, we demonstrated that autophagy facilitated DTMUV replication, aggravated the developments of pathological symptoms and possibly counteracts the host's innate immunity response in vivo.

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“…Altered lipid metabolism is linked to the life cycle of HCV considering that virions coated with lipoproteins facilitate hepatocyte entry via lipoprotein receptors, however, the HCV-induced ER-stress leads to steatosis [3]. Intracellular lipid droplets being in excess in the cells are degraded by an autophagy process called lipophagy [3][4][5]22]. Vescovo et al reported that autophagy acts against the alterations in lipid metabolism induced by HCV and steatosis may develop when autophagy is disrupted [39].…”

Section: Discussionmentioning

confidence: 99%

“…Despite the remarkable healing effect of the newly introduced direct-acting antivirals (DAAs), several issues are still not resolved or are under dispute [2,3]. One of these is the role autophagy may play in the pathogenesis of chronic hepatitis C (CHC), which has been in the focus of several recent studies [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Cell growth, development and homeostasis are the major processes in which autophagy is involved in order to maintain the balance between synthesis, degradation, and subsequent recycling of cellular products [7]. Several stress factors, including viral infection and autoimmunity, are known to activate autophagy [4,8,9]. Selective mitochondrial autophagy, termed mitophagy is particularly important in the elimination of mitochondrial dysfunction arising from aging and damage, thus, mitophagy plays crucial role in the reduction of oxidative stress and maintenance of cellular homeostasis [4,6,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Szekerczés

Gógl

Illyés

et al. 2020

Pathol. Oncol. Res.

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Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and − 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and − 155 seem to be associated with CHC progression.

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The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions

Cited by 48 publications

References 520 publications

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

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