Division of Dermatology, Department of Medicine, University of California-San Diego, La Jolla, California 92093, USA.
Nat Commun. 2013;4:1963. doi: 10.1038/ncomms2963.
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.
单纯疱疹病毒 1 型是一种重要的上皮病原体，在人类中有很大的发病风险。在这里，我们证明了一种细胞表面清道夫受体，即具有胶原结构的巨噬细胞受体（MARCO），以前被认为通过识别核酸来增强抗病毒防御能力，但它被单纯疱疹病毒 1 型劫持，并与硫酸乙酰肝素蛋白聚糖一起发挥作用，介导对上皮细胞的吸附。MARCO 的配体可显著抑制单纯疱疹病毒 1 型对人角质形成细胞的吸附和感染，并可保护小鼠免受感染。单纯疱疹病毒 1 型糖蛋白 C 与 MARCO 在细胞表面紧密共定位，并且糖蛋白 C 以高亲和力直接与纯化的 MARCO 结合。增加 MARCO 的表达会增强单纯疱疹病毒 1 型的感染，而 MARCO(-/-) 小鼠对单纯疱疹病毒 1 型感染的敏感性降低。这些发现表明单纯疱疹病毒 1 型结合 MARCO 来增强其疾病能力，并为改变单纯疱疹病毒 1 型在皮肤感染中的致病性提供了一个新的治疗靶点。
