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Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor.
Stichling, Nicole Suomalainen, Maarit Flatt, Justin W Schmid, Markus Pacesa, Martin Hemmi, Silvio Jungraithmayr, Wolfgang Maler, Mareike D Freudenberg, Marina A Plückthun, Andreas
Stichling, Nicole
Suomalainen, Maarit
Flatt, Justin W
Schmid, Markus
Pacesa, Martin
Hemmi, Silvio
Jungraithmayr, Wolfgang
Maler, Mareike D
Freudenberg, Marina A
Plückthun, Andreas
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2018-03
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Abstract
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.
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Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor. 2018, 14 (3):e1006914 PLoS Pathog.
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en
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1553-7374