ArticleProceedings of the National Academy of Sciences of the United States of America2016
Hepatitis C virus promotes virion secretion through cleavage of the Rab7 adaptor protein RILP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- The Arg/N-degron pathway mediates the secretion of apoptotic exosomes under oxidative stress in cancer cell.iScience · 2025Article
- RILP cleavage links an inflammatory state to enhanced tau propagation in a cell culture model of Alzheimer's disease.Molecular biology of the cell · 2025Article
- Virus infection and vesicle trafficking.Frontiers in immunology · 2025Review
- Molecular basis for the assembly of the dynein transport machinery on microtubules.bioRxiv : the preprint server for biology · 2024Article
- An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal.Autophagy · 2024Article
- The Regulation of Exosome Generation and Function in Physiological and Pathological Processes.International journal of molecular sciences · 2023Review
- The Early Secretory Pathway Is Crucial for Multiple Aspects of the Hepatitis C Virus Life Cycle.Journal of virology · 2023Article
- Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus.PLoS pathogens · 2023Article
- Inflammatory macrophage to hepatocyte signals can be prevented by extracellular vesicle reprogramming.Journal of cell science · 2023Article
- A genome-wide optical pooled screen reveals regulators of cellular antiviral responses.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Current Knowledge on Exosome Biogenesis, Cargo-Sorting Mechanism and Therapeutic Implications.Membranes · 2022Review
- Mechanism of cargo sorting into small extracellular vesicles.Bioengineered · 2021Article
- Tombusviruses Target a Major Crossroad in the Endocytic and Recycling Pathways via Co-opting Rab7 Small GTPase.Journal of virology · 2021Article
- Review
- Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System.Journal of personalized medicine · 2021Review
- Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain.Scientific reports · 2021Article
- The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation.The Journal of cell biology · 2020Article
- The Dynein Adaptor RILP Controls Neuronal Autophagosome Biogenesis, Transport, and Clearance.Developmental cell · 2020Article
- Hepatitis C virus infection increases autophagosome stability by suppressing lysosomal fusion through an Arl8b-dependent mechanism.The Journal of biological chemistry · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) is an enveloped RNA virus that modifies intracellular trafficking processes. The mechanisms that HCV and other viruses use to modify these events are poorly understood. In this study, we observed that two different RNA viruses, HCV and Sendai, cause inhibition of ras-related protein Rab-7 (Rab7)-dependent endosome-lysosome fusion. In both cases, viral infection causes cleavage of the Rab7 adaptor protein RILP (Rab interacting lysosomal protein), which is responsible for linking Rab7 vesicles to dynein motor complexes. RILP cleavage results in the generation of a cleaved RILP fragment (cRILP) missing the N terminus of the molecule. Although RILP localizes in a perinuclear fashion, cRILP moves to the cell periphery. Both knockdown of RILP and expression of cRILP reproduced the HCV-induced trafficking defect, and restoring full-length RILP reversed the trafficking effects of virus. For the first 3 d after electroporation of HCV RNA, intracellular virus predominates over secreted virus, but the quantity of intracellular virus then rapidly declines as secreted virus dominates. The transition from the intracellular-predominant to the secretion-predominant phenotype corresponds to the time course of cRILP generation. Expressing cRILP directly prevents intracellular virus accumulation at early times without affecting net virus production. The ability of cRILP to promote virus secretion could be prevented by a kinesin inhibitor. HCV thus modifies cellular trafficking by cleaving RILP, which serves to redirect Rab7-containing vesicles to a kinesin-dependent trafficking mode promoting virion secretion. Cleavage of a Rab adaptor protein is thus a mechanism by which viruses modify trafficking patterns of infected cells.
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