ArticleMolecular and cellular biology2015
Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- The relationship between HIV-1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post-mortem brain tissue.Reviews in medical virology · 2024Pooled it
- Epithelial PCSK6 Promotes Proliferation and Decreases Collagen Deposition by Fibroblasts Potentially via MMP Activation.International journal of molecular sciences · 2026Article
- Review
- Host antiviral factors hijack furin to block SARS-CoV-2, ebola virus, and HIV-1 glycoproteins cleavage.Emerging microbes & infections · 2023Review
- The emerging roles of MARCH8 in viral infections: A double-edged Sword.PLoS pathogens · 2023Review
- Inhibition of Infectious HIV-1 Production by Rerouting the Cellular Furin Inhibitor Serpin B8.Journal of virology · 2023Article
- Reply to Spek and Duitman.American journal of respiratory and critical care medicine · 2023Article
- PCSK6: The Endogenous PAR-1 Agonist Driving Pulmonary Fibrosis?American journal of respiratory and critical care medicine · 2023Article
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- Article
- How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?Viruses · 2021Review
- GPR37 is processed in the N-terminal ectodomain by ADAM10 and furin.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin.Journal of biomolecular structure & dynamics · 2021Review
- Role of Thrombin in Central Nervous System Injury and Disease.Biomolecules · 2021Review
- Shedding of cancer susceptibility candidate 4 by the convertases PC7/furin unravels a novel secretory protein implicated in cancer progression.Cell death & disease · 2020Article
- Lysosome-Associated Membrane Proteins Support the Furin-Mediated Processing of the Mumps Virus Fusion Protein.Journal of virology · 2020Article
- The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.Antiviral research · 2020Article
- HIV-induced neuroinflammation: impact of PAR1 and PAR2 processing by Furin.Cell death and differentiation · 2019Article
- Article
- Furin-mediated protein processing in infectious diseases and cancer.Clinical & translational immunology · 2019Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND.
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Registered trials
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