ArticleAutophagy2013
Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (MTOR) pathway, through endoplasmic reticulum stress to induce autophagy.
Article in Autophagy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 133 citations in OpenAlex.
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- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- The molecular mechanisms of autophagy-virus interactions: from antiviral defense to viral counterstrategies.FEMS microbiology reviews · 2026Review
- A Focus on Natural Autophagy Modulators as Potential Host-Directed Weapons Against Emerging and Re-Emerging Viruses.Medicinal research reviews · 2025Review
- NSP6 of SARS-CoV-2 Dually Regulates Autophagic-Lysosomal Degradation.International journal of molecular sciences · 2025Article
- AMPK activation by hepatitis E virus infection inhibits viral replication through attenuation of autophagosomes and promotion of innate immunity.Cellular and molecular life sciences : CMLS · 2025Article
- Effect of the CSFV NS5A protein on key proteins in the MAPK and PI3K-mTOR signaling pathways in porcine macrophages.Frontiers in microbiology · 2025Article
- Viruses and autophagy: bend, but don't break.Nature reviews. Microbiology · 2024Review
- Autophagy modulates physiologic and adaptive response in the liver.Liver research (Beijing, China) · 2023Review
- Insights from a Computational-Based Approach for Analyzing Autophagy Genes across Human Cancers.Genes · 2023Review
- Porcine Epidemic Diarrhea Virus and Its nsp14 Suppress ER Stress Induced GRP78.International journal of molecular sciences · 2023Article
- The role of autophagy in viral infections.Journal of biomedical science · 2023Review
- Canonical and Noncanonical ER Stress-Mediated Autophagy Is a Bite the Bullet in View of Cancer Therapy.Cells · 2022Review
- The Function behind the Relation between Lipid Metabolism and Vimentin on H9N2 Subtype AIV Replication.Viruses · 2022Article
- The molecular regulation of autophagy in antimicrobial immunity.Journal of molecular cell biology · 2022Article
- PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy.Immunologic research · 2022Review
- Synergetic Contributions of Viral VP1, VP3, and 3C to Activation of the AKT-AMPK-MAPK-MTOR Signaling Pathway for Seneca Valley Virus-Induced Autophagy.Journal of virology · 2022Article
- Non-Structural Protein 3 of Duck Tembusu Virus Induces AutophagyFrontiers in immunology · 2022Article
- Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.PLoS pathogens · 2022Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) is able to induce autophagy via endoplasmic reticulum (ER) stress, but the exact molecular signaling pathway is not well understood. We found that the activity of the mechanistic target of rapamycin complex 1 (MTORC1) was inhibited in Huh7 cells either harboring HCV-N (genotype 1b) full-genomic replicon or infected with JFH1 (genotype 2a) virus, which led to the activation of UNC-51-like kinase 1 (ULK1) and thus to autophagy. We then analyzed activity upstream of MTORC1, and found that both protein kinase, AMP-activated, α (PRKAA, including PRKAA1 and PRKAA2, also known as AMP-activated protein kinase, AMPKα) and AKT (refers to pan AKT, including three isoforms of AKT1-3, also known as protein kinase B, PKB) were inhibited by HCV infection. The inhibition of the AKT-TSC-MTORC1 pathway contributed to upregulating autophagy, but inhibition of PRKAA downregulated autophagy. The net effect on autophagy was from AKT, which overrode the inhibition effect from PRKAA. It was further found that HCV-induced ER stress was responsible for the inhibition of the AKT pathway. Metformin, a PRKAA agonist, inhibited HCV replication not only by activating PRKAA as previously reported, but also by activating AKT independently of the autophagy pathway. Taken together, our data suggested HCV inhibited the AKT-TSC-MTORC1 pathway via ER stress, resulting in autophagy, which may contribute to the establishment of the HCV-induced autophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.