%0 Journal Article %T Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor %A Andreas Pl¨¹ckthun %A Gy£¿rgy Fejer %A Justin W. Flatt %A Maarit Suomalainen %A Mareike D. Maler %A Marina A. Freudenberg %A Mario K£¿ster %A Markus Schmid %A Martin Pacesa %A Nicole Stichling %A Silvio Hemmi %A Tobias May %A Urs F. Greber %A Wolfgang Jungraithmayr %J - %D 2018 %R 10.1371/journal.ppat.1006914 %X 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 %K Cell binding %K Antibodies %K Virions %K Alveolar macrophages %K Macrophages %K Cell binding assay %K Adenoviruses %K Transfection %U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006914