title: HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection.
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.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California-San Diego, La Jolla, California 92093, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: MacLeod
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nakatsuji
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000327:Adsorption; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000302:isolation & purification / Q000378:metabolism; D014771:Virion / Q000378:metabolism
chemical_list: D008024:Ligands; C490460:MARCO protein, human; C092228:Marco protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1