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

Nicole Stichling1,2, Maarit Suomalainen1, Justin W Flatt1

  • 1Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Plos Pathogens
|March 10, 2018
PubMed

Insights

Scavenger receptor SR-A6 acts as an entry point for human adenoviruses in macrophages, crucial for innate immunity. This finding enhances understanding of viral entry and host defense mechanisms.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Macrophages are key immune cells involved in pathogen defense.
  • Scavenger receptors play roles in clearing cellular debris and pathogens.
  • Human adenoviruses are significant human pathogens and viral vectors.

Purpose of the Study:

  • To identify the specific entry receptor for human adenoviruses on macrophages.
  • To elucidate the role of scavenger receptors in adenovirus infection and innate immunity.
  • To investigate the interaction between scavenger receptor SR-A6 and human adenoviruses.

Main Methods:

  • Utilized murine alveolar macrophage-like MPI cells and knockout/inhibition strategies for SR-A6.
  • Employed adenovirus type-C5 (HAdV-C5) for binding and transduction assays.
  • Investigated the role of hexon's hypervariable region 1 (HVR1) in viral binding.
  • Assessed the function of SR-A6 with other adenovirus serotypes (HAdV-B35, HAdV-D26).

Main Results:

  • SR-A6 was identified as a crucial entry receptor for HAdV-C5 on MPI cells.
  • Blocking SR-A6 function (knockout, antibody, soluble domain) reduced HAdV-C5 binding and transduction.
  • Expression of SR-A6 enhanced HAdV binding and transduction in human cells.
  • The hexon protein's HVR1 was implicated as the viral ligand for SR-A6.
  • SR-A6 also facilitated entry of HAdV-B35 and HAdV-D26 into macrophages.

Conclusions:

  • Scavenger receptor SR-A6 is a key receptor mediating human adenovirus entry into macrophages.
  • SR-A6 plays a significant role in the innate immune response against adenoviruses.
  • This discovery has implications for understanding viral infections and developing adenovirus-based gene therapy and vaccination strategies.

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