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

Daniel T. MacLeod, Teruaki Nakatsuji, Kenshi Yamasaki, Lester Kobzik and Richard L. Gallo ()
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Daniel T. MacLeod: University of California–San Diego
Teruaki Nakatsuji: University of California–San Diego
Kenshi Yamasaki: University of California–San Diego
Lester Kobzik: Harvard School of Public Health
Richard L. Gallo: University of California–San Diego

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2963

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