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Open Access | 10.1172/jci.insight.144255
1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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Li, J.
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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Finn, P.
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1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, United States of America
2Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, United States of America
3Department of Dermatology, Northwestern University, Chicago, United States of America
4Department of Psychiatry, University of Illinois at Chicago, Chicago, United States of America
5Department of Pharmacology, University of California San Diego, La Jolla, United States of America
6Rappaport Faculty of Medicine, Haifa, Israel
7Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden
8Department of Medicine, University of Illinois at Chicago, Chicago, United States of America
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Published February 23, 2021 - More info
The drive to withstand environmental stresses and defend against invasion is a universal trait extant in all forms of life. While numerous canonical signaling cascades have been characterized in detail, it remains unclear how these pathways interface to generate coordinated responses to diverse stimuli. To dissect these connections, we follow heparanase (HPSE), a protein best known for its endoglycosidic activity at the extracellular matrix but recently recognized to drive various forms of late stage disease through unknown mechanisms. Using herpes simplex virus-1 (HSV-1) infection as a model cellular perturbation, we demonstrate that HPSE acts beyond its established enzymatic role to restrict multiple forms of cell-intrinsic defense and facilitate host cell reprogramming by the invading pathogen. We reveal that cells devoid of HPSE are innately resistant to infection and counteract viral takeover through multiple amplified defense mechanisms. With a unique grasp of the fundamental processes of transcriptional regulation and cell death, HPSE represents a potent cellular intersection with broad therapeutic potential.
View Dataset S1. Transcriptomics count matrices
View Dataset S2. Baseline transcriptomics differential expression
View Dataset S3. Results of clustered transcriptomics ClueGO gene ontology analysis
View Dataset S4. Results of baseline transcriptomics ClueGO gene ontology analysis
View Dataset S5. Quantitative proteomics normalized expression matrix