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Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor
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Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor
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Journal Article
Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor
2018
Overview
Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Adenoviridae Infections - immunology
/ Adenoviridae Infections - metabolism
/ Adenoviridae Infections - virology
/ Adenoviruses, Human - immunology
/ Alveoli
/ Animals
/ Binding
/ Grants
/ Humans
/ Immunity
/ Lungs
/ Macrophages, Alveolar - immunology
/ Macrophages, Alveolar - metabolism
/ Macrophages, Alveolar - virology
/ Medicine
/ Medicine and Health Sciences
/ Mice
/ Proteins
/ Receptors, Immunologic - genetics
/ Receptors, Immunologic - metabolism
/ Receptors, Immunologic - physiology
/ Research and Analysis Methods
/ Vectors
/ Virions
/ Viruses
