ArticleJournal of virology2019
Nir2 Is an Effector of VAPs Necessary for Efficient Hepatitis C Virus Replication and Phosphatidylinositol 4-Phosphate Enrichment at the Viral Replication Organelle.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Reciprocal control of viral infection and phosphoinositide dynamics.FEBS letters · 2026Review
- Disrupted glycosylphosphatidylinositol anchoring induces ER stress and restricts enterovirus infection.PLoS pathogens · 2025Article
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- The class III phosphatidylinositol 3-kinase VPS34 supports EV71 replication by promoting viral replication organelle formation.Journal of virology · 2024Article
- Mammalian START-like phosphatidylinositol transfer proteins - Physiological perspectives and roles in cancer biology.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Review
- Viral regulation of organelle membrane contact sites.PLoS biology · 2024Article
- N-terminal acetyltransferase 6 facilitates enterovirus 71 replication by regulating PI4KB expression and replication organelle biogenesis.Journal of virology · 2024Article
- Coordination of oxysterol binding protein 1 and VAP-A/B modulates the generation of cholesterol and viral inclusion bodies to promote grass carp reovirus replication.Frontiers in immunology · 2024Article
- Phosphoinositides as membrane organizers.Nature reviews. Molecular cell biology · 2022Review
- Ebola Virus Encodes Two microRNAs in Huh7-Infected Cells.International journal of molecular sciences · 2022Article
- VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.Frontiers in cell and developmental biology · 2022Review
- Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation.Nature communications · 2021Article
- Courier service for phosphatidylinositol: PITPs deliver on demand.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- Emerging perspectives on multidomain phosphatidylinositol transfer proteins.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- Hepatitis C Virus Uses Host Lipids to Its Own Advantage.Metabolites · 2021Review
- Role of Lipid Transfer Proteins (LTPs) in the Viral Life Cycle.Frontiers in microbiology · 2021Review
- Reverse Genetic Approaches for the Generation of Full Length and Subgenomic Replicon of EV71 Virus.Frontiers in microbiology · 2021Article
- Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses.Biochimie · 2020Review
- Whole Lotta Lipids-from HCV RNA Replication to the Mature Viral Particle.International journal of molecular sciences · 2020Review
- Lipid Exchangers: Cellular Functions and Mechanistic Links With Phosphoinositide Metabolism.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
The endoplasmic reticulum (ER)-resident proteins vesicle-associated membrane protein (VAMP)-associated protein A and B (VAPA and VAPB) have been reported to be necessary for efficient hepatitis C virus (HCV) replication, but the specific mechanisms are not well understood. VAPs are known to recruit lipid transfer proteins to the ER, including oxysterol binding protein (OSBP), which has been previously shown to be necessary for cholesterol delivery to the HCV replication organelle in exchange for phosphatidylinositol 4-phosphate [PI(4)P]. Here, we show that VAPA and VAPB are redundant for HCV infection and that dimerization is not required for their function. In addition, we identify the phosphatidylinositol transfer protein Nir2 as an effector of VAPs to support HCV replication. We propose that Nir2 functions to replenish phosphoinositides at the HCV replication organelle to maintain elevated steady-state levels of PI(4)P, which is removed by OSBP. Thus, Nir2, along with VAPs, OSBP, and the phosphatidylinositol 4-kinase, completes a cycle of phosphoinositide flow between the ER and viral replication organelles to drive ongoing viral replication.
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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.