Journal
PLOS PATHOGENS
Volume 14, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1006914
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Funding
- Swiss National Science Foundation [3100306_160316, Sinergia CRSII5_170929/1, R'Equip 316030_170799/1, 31003A_146286]
- Initial Training Network grant - FP7 of the European Commission [290002 ADVance]
- Human Frontier Science Program [000348/2014-L]
- National Centre for the Replacement, Refinement and Reduction of Animals in Research UK [NC3Rs NC/L00058X/1]
- FSR grant Sarcoidosis Disease Model
- Swiss National Science Foundation (SNF) [31003A_146286] Funding Source: Swiss National Science Foundation (SNF)
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/L00058X/1] Funding Source: researchfish
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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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