Autophagy in HCV Replication and Protein Trafficking

Chu, Ja Yeon Kim; Ou, Jing-Hsiung

doi:10.3390/ijms22031089

Cited by 17 publications

(8 citation statements)

References 67 publications

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“…Moreover, HBx-mediated autophagy has also been demonstrated to play an important role in NFkB-dependent production of pro-inflammatory cytokines, such as interleukin (IL)-6 or IL-8 that are two predictors of HCC progression in patients suffering from chronic hepatitis infection (95,96). As previously described, HCV-encoded NS4B protein induces rubicon expression, leading to the inhibition of autophagosomes maturation (97,98). Autophagy inhibition leads to an accumulation of the autophagy receptor p62 in HCV-associated HCC patients.…”

Section: Oncogenic Viruses and Autophagy Inhibitionmentioning

confidence: 88%

Autophagy Modulation by Viral Infections Influences Tumor Development

et al. 2021

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Autophagy is a self-degradative process important for balancing cellular homeostasis at critical times in development and/or in response to nutrient stress. This is particularly relevant in tumor model in which autophagy has been demonstrated to have an important impact on tumor behavior. In one hand, autophagy limits tumor transformation of precancerous cells in early stage, and in the other hand, it favors the survival, proliferation, metastasis, and resistance to antitumor therapies in more advanced tumors. This catabolic machinery can be induced by an important variety of extra- and intracellular stimuli. For instance, viral infection has often been associated to autophagic modulation, and the role of autophagy in virus replication differs according to the virus studied. In the context of tumor development, virus-modulated autophagy can have an important impact on tumor cells’ fate. Extensive analyses have shed light on the molecular and/or functional complex mechanisms by which virus-modulated autophagy influences precancerous or tumor cell development. This review includes an overview of discoveries describing the repercussions of an autophagy perturbation during viral infections on tumor behavior.

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Section: Oncogenic Viruses and Autophagy Inhibitionmentioning

confidence: 88%

Autophagy Modulation by Viral Infections Influences Tumor Development

et al. 2021

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“…The association of autophagy with HCV infection is highly significant in IR development. It may be induced by one or more of the viral nonstructural proteins (NS3-5B) [ 56 , 73 ]. Progression of the autophagic process may increase viral replication by providing a double-membrane structure of autophagic vacuoles [ 12 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

GSK-3β as a Potential Coordinator of Anabolic and Catabolic Pathways in Hepatitis C Virus Insulin Resistance

Das,

Hollinger

2023

Intervirology

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Introduction: Chronic HCV infection results in insulin resistance (IR) through interaction of pathways for glucose homeostasis, insulin signaling, and autophagy. Not known is how soon the pathways are activated, and how IR is related to the signals generated by catabolic and anabolic conditions occurring in infected cells. We have extended our studies to a cell culture system mimicking acute infection and to downstream pathways involving energy-sensor AMPK and nutrient-sensor mTOR that are active in catabolic and anabolic processes within the infected cells. Methods: Huh7 liver cells were infected with HCV. We performed proteomics analysis of key proteins in infected cells by western blotting and IP experiments, with or without interferon-α exposure. Results: We show that IRS-1 Ser312, Beclin-1, protein conjugate Atg12-Atg5 or GS Ser641 are upregulated early in infection by activating the same pathways utilized for persistent infection; Bcl-XL, an inhibitor of both autophagy and apoptosis, is present in a core-complex with IRS-1 Ser312 and Beclin-1 during progression of IR; AMPK level remains the same in infected cells where it is activated by phosphorylation at Thr172 concomitant with increased autophagy, a hallmark of catabolic conditions; an mTOR level that promotes anabolism is increased rather than decreased under an expanded autophagy; hypophosphorylation of translational repressor 4E-BP1 downstream of mTOR is suggestive of reduced protein synthesis; and β-catenin is upregulated but not phosphorylated suggesting indirectly our previous contention that its kinase, GSK-3β, is mostly in an inactive state. Discussion/Conclusion: We report that in the development of IR following chronic infection, anabolic and catabolic pathways are activated early, and the metabolic interaction occurs possibly in a core-complex with IRS-1 Ser312, Beclin-1 and autophagy inhibitor BcL-XL. Induction of autophagy is usually controlled by a two-edged mechanism acting in opposition under anabolic and catabolic conditions by AMPK/mTOR/4E-BP1 pathways with GSK-3β mediated feed-back loops. However, we observed that an up-regulation of mTOR along with an up-regulation of AMPK caused by HCV infection is a deviation from the normal scenario described above which might be of therapeutic interest.

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“…Autophagy inhibition also abrogates HBx-induced activation of nuclear factor-κB (NF-κB) and production of interleukin-6 (IL-6), IL-8, and CXCL2 ( 44 ). Similarly, autophagy is required to promote HCV replication, partly through suppression of innate immunity ( 45 , 46 ). HCV-induced autophagy can suppress host innate immune response through autophagic degradation of TRAF6, which is an important signaling molecule that mediates the activation of NF-kB and expression of cytokines and interferons ( 47 ).…”

Section: Autophagy Dysregulation In Hepatocytes Leads To Liver Inflam...mentioning

confidence: 99%

Hepatocytes: A key role in liver inflammation

Gong

Liu

et al. 2023

Front. Immunol.

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Hepatocytes, the major parenchymal cells in the liver, are responsible for a variety of cellular functions including carbohydrate, lipid and protein metabolism, detoxification and immune cell activation to maintain liver homeotasis. Recent studies show hepatocytes play a pivotal role in liver inflammation. After receiving liver insults and inflammatory signals, hepatocytes may undergo organelle damage, and further respond by releasing mediators and expressing molecules that can act in the microenvironment as well as initiate a robust inflammatory response. In this review, we summarize how the hepatic organelle damage link to liver inflammation and introduce numerous hepatocyte-derived pro-inflammatory factors in response to chronic liver injury.

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Autophagy in HCV Replication and Protein Trafficking

Cited by 17 publications

References 67 publications

Autophagy Modulation by Viral Infections Influences Tumor Development

Autophagy Modulation by Viral Infections Influences Tumor Development

GSK-3β as a Potential Coordinator of Anabolic and Catabolic Pathways in Hepatitis C Virus Insulin Resistance

Hepatocytes: A key role in liver inflammation

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