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

Daniel T. MacLeod; Teruaki Nakatsuji; Kenshi Yamasaki; Lester Kobzik; Richard L. Gallo

doi:10.1038/ncomms2963

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

Daniel T. MacLeod, Teruaki Nakatsuji, Kenshi Yamasaki, Lester Kobzik, Richard L. Gallo

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

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.

Original language	English
Article number	1963
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2963
Publication status	Published - 2013 Jun 6

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms2963

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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.",

author = "MacLeod, {Daniel T.} and Teruaki Nakatsuji and Kenshi Yamasaki and Lester Kobzik and Gallo, {Richard L.}",

note = "Funding Information: We would like to thank Dr Roselyn Eisenberg and Dr Gary Cohen (University of Pennsylvania, PA), Dr Harvey Friedman (University of Pennsylvania, PA), Dr Andrij Holian (Univerity of Montana, MT), Dr Rivkah Isseroff (University of California, Davis, CA) and Dr William Fenical (Scripps Institute of Oceanography, CA) for providing us with key reagents as described in the Methods section. We would like to thank Deborah Spector (University of California, San Diego) for critical review of our manuscript. Portions of this work were supported by The Atopic Dermatitis Research Network (ADRN) (HHSN272201000020C), an NIH Institutional T32 grant (T32 AR062496) supporting D.T.M., and NIH grants R01 AR052728, R01 AI052453, R01 AI0833358 to R.L.G. and RO1 ES11008 (to L.K.). Publisher Copyright: {\textcopyright} 2013 Macmillan Publishers Limited. All rights reserved.",

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AU - MacLeod, Daniel T.

AU - Nakatsuji, Teruaki

AU - Yamasaki, Kenshi

AU - Kobzik, Lester

AU - Gallo, Richard L.

N1 - Funding Information: We would like to thank Dr Roselyn Eisenberg and Dr Gary Cohen (University of Pennsylvania, PA), Dr Harvey Friedman (University of Pennsylvania, PA), Dr Andrij Holian (Univerity of Montana, MT), Dr Rivkah Isseroff (University of California, Davis, CA) and Dr William Fenical (Scripps Institute of Oceanography, CA) for providing us with key reagents as described in the Methods section. We would like to thank Deborah Spector (University of California, San Diego) for critical review of our manuscript. Portions of this work were supported by The Atopic Dermatitis Research Network (ADRN) (HHSN272201000020C), an NIH Institutional T32 grant (T32 AR062496) supporting D.T.M., and NIH grants R01 AR052728, R01 AI052453, R01 AI0833358 to R.L.G. and RO1 ES11008 (to L.K.). Publisher Copyright: © 2013 Macmillan Publishers Limited. All rights reserved.

PY - 2013/6/6

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N2 - 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.

AB - 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.

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

Abstract

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UN SDGs

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