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

被引：41
作者：
MacLeod, Daniel T. [1 ]
Nakatsuji, Teruaki [1 ,2 ]
Yamasaki, Kenshi [1 ]
Kobzik, Lester [3 ]
Gallo, Richard L. [1 ,2 ]
机构：
[1] Univ Calif San Diego, Dept Med, Div Dermatol, La Jolla, CA 92093 USA
[2] Veterans Affairs San Diego Hlth Care Syst, San Diego, CA 92161 USA
[3] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA
来源：
NATURE COMMUNICATIONS | 2013年 / 4卷
关键词：
HERPES-SIMPLEX-VIRUS; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTOR-3; LOW-DENSITY-LIPOPROTEIN; HEPARAN-SULFATE; GLYCOPROTEIN-C; EPIDERMAL-KERATINOCYTES; ADAPTER MOLECULE; TLR3; DEFICIENCY; ENTRY;
D O I：
10.1038/ncomms2963
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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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页数：9
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