%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