TY - JOUR
T1 - Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor
AU - Stichling, Nicole
AU - Suomalainen, Maarit
AU - Flatt, Justin W.
AU - Schmid, Markus
AU - Pacesa, Martin
AU - Hemmi, Silvio
AU - Jungraithmayr, Wolfgang
AU - Maler, Mareike D.
AU - Freudenberg, Marina A.
AU - Plückthun, Andreas
AU - May, Tobias
AU - Köster, Mario
AU - Fejer, György
AU - Greber, Urs F.
N1 - Publisher Copyright:
© 2018 Stichling et al.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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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U2 - 10.1371/journal.ppat.1006914
DO - 10.1371/journal.ppat.1006914
M3 - Article
C2 - 29522575
AN - SCOPUS:85044816646
SN - 1553-7366
VL - 14
JO - PLoS pathogens
JF - PLoS pathogens
IS - 3
M1 - e1006914
ER -