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HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection

Author

Listed:
  • Daniel T. MacLeod

    (University of California–San Diego)

  • Teruaki Nakatsuji

    (University of California–San Diego
    Veterans Affairs San Diego Health Care System)

  • Kenshi Yamasaki

    (University of California–San Diego)

  • Lester Kobzik

    (Harvard School of Public Health)

  • Richard L. Gallo

    (University of California–San Diego
    Veterans Affairs San Diego Health Care System)

Abstract

Herpes simplex virus type 1 is an important epithelial pathogen and has the potential for significant morbidity in humans. Here we demonstrate that a cell surface scavenger receptor, macrophage receptor with collagenous structure (MARCO), previously thought to enhance antiviral defense by enabling nucleic acid recognition, is usurped by herpes simplex virus type 1 and functions together with heparan sulphate proteoglycans to mediate adsorption to epithelial cells. Ligands of MARCO dramatically inhibit herpes simplex virus type 1 adsorption and infection of human keratinocytes and protect mice against infection. Herpes simplex virus type 1 glycoprotein C closely co-localizes with MARCO at the cell surface, and glycoprotein C binds directly to purified MARCO with high affinity. Increasing MARCO expression enhances herpes simplex virus type 1 infection while MARCO−/− mice have reduced susceptibility to infection by herpes simplex virus type 1. These findings demonstrate that herpes simplex virus type 1 binds to MARCO to enhance its capacity for disease, and suggests a new therapeutic target to alter pathogenicity of herpes simplex virus type 1 in skin infection.

Suggested Citation

  • Daniel T. MacLeod & Teruaki Nakatsuji & Kenshi Yamasaki & Lester Kobzik & Richard L. Gallo, 2013. "HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2963
    DOI: 10.1038/ncomms2963
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