ArticlemBio2018
Interactions between the Hepatitis C Virus Nonstructural 2 Protein and Host Adaptor Proteins 1 and 4 Orchestrate Virus Release.
Article in mBio, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.European journal of medicinal chemistry · 2025Article
- Pathogenicity and virulence of Powassan virus.Virulence · 2025Review
- Virus infection and vesicle trafficking.Frontiers in immunology · 2025Review
- Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient virion production.Journal of virology · 2024Article
- Landscape of protein-protein interactions during hepatitis C virus assembly and release.Microbiology spectrum · 2024Article
- Review
- Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes.Thyroid : official journal of the American Thyroid Association · 2022Article
- Characterization of a multipurpose NS3 surface patch coordinating HCV replicase assembly and virion morphogenesis.PLoS pathogens · 2022Article
- Acidic dileucine motifs in the cylindrical inclusion protein of turnip mosaic virus are crucial for endosomal targeting and viral replication.Molecular plant pathology · 2022Article
- Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies.Antiviral research · 2022Article
- The cargo adapter protein CLINT1 is phosphorylated by the Numb-associated kinase BIKE and mediates dengue virus infection.The Journal of biological chemistry · 2022Article
- Cellular host factors for SARS-CoV-2 infection.Nature microbiology · 2021Review
- Cellular factors involved in the hepatitis C virus life cycle.World journal of gastroenterology · 2021Review
- Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species.International journal of molecular sciences · 2021Review
- BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.Antiviral research · 2020Article
- The Serine/Threonine Kinase AP2-Associated Kinase 1 Plays an Important Role in Rabies Virus Entry.Viruses · 2019Article
- Article
- Synthesis and Structure-Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3- b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity.Journal of medicinal chemistry · 2019Article
- Viral journeys on the intracellular highways.Cellular and molecular life sciences : CMLS · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly. We demonstrated that the host kinases AAK1 and GAK regulate HCV infection by controlling these clathrin-associated APs. Here, we sought to define the roles of AP-4, a clathrin-independent adaptor; AP-1A; and AP-1B in HCV infection. We screened for interactions between HCV proteins and the μ subunits of AP-1A, AP-1B, and AP-4 by mammalian cell-based protein fragment complementation assays. The nonstructural 2 (NS2) protein emerged as an interactor of these adaptors in this screening and by coimmunoprecipitations in HCV-infected cells. Two previously unrecognized dileucine-based motifs in the NS2 C terminus mediated AP binding and HCV release. Infectivity and coculture assays demonstrated that while all three adaptors mediate HCV release and cell-free spread, AP-1B and AP-4, but not AP-1A, mediate cell-to-cell spread. Live-cell imaging revealed HCV cotrafficking with AP-1A, AP-1B, and AP-4 and that AP-4 mediates HCV trafficking in a post-Golgi compartment. Lastly, HCV cell-to-cell spread was regulated by AAK1 and GAK and thus susceptible to treatment with AAK1 and GAK inhibitors. These data provide a mechanistic understanding of HCV trafficking in distinct release pathways and reveal a requirement for APs in cell-to-cell viral spread.
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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.