PLoS Pathogens (Mar 2018)

Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor.

  • Nicole Stichling,
  • Maarit Suomalainen,
  • Justin W Flatt,
  • Markus Schmid,
  • Martin Pacesa,
  • Silvio Hemmi,
  • Wolfgang Jungraithmayr,
  • Mareike D Maler,
  • Marina A Freudenberg,
  • Andreas Plückthun,
  • Tobias May,
  • Mario Köster,
  • György Fejer,
  • Urs F Greber

DOI
https://doi.org/10.1371/journal.ppat.1006914
Journal volume & issue
Vol. 14, no. 3
p. e1006914

Abstract

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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.