de Jong Marein A W P, de Witte Lot, Bolmstedt Anders, van Kooyk Yvette, Geijtenbeek Teunis B H
Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Department of Clinical Virology, University of Göteborg, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden.
J Gen Virol. 2008 Oct;89(Pt 10):2398-2409. doi: 10.1099/vir.0.2008/003129-0.
Dendritic cells (DCs) are essential for the induction of specific immune responses against invading pathogens. Herpes simplex virus (HSV) is a common human pathogen that causes painful but mild infections of the skin and mucosa, and which results in latency and recurrent infections. Of the two HSV subtypes described, HSV-1 causes mainly oral-facial lesions, whilst HSV-2 is associated with genital herpes. DCs are involved in HSV-induced immune suppression, but little is known about the molecular interactions between DCs and HSV. This study demonstrated that HSV-1 and -2 both interact with the DC-specific C-type lectin DC-SIGN. Further analyses demonstrated that DC-SIGN interacts with the HSV glycoproteins gB and gC. Binding of HSV-1 to immature DCs depended on both DC-SIGN and heparan sulfate proteoglycans. Strikingly, HSV-1 infection of DCs was almost completely inhibited by blocking antibodies against DC-SIGN. Thus, DC-SIGN is an important attachment receptor for HSV-1 on immature DCs and enhances infection of DCs in cis. In addition, DC-SIGN captures HSV-1 for transmission to permissive target cells. These data strongly suggest that DC-SIGN is a potential target to prevent HSV infection and virus dissemination. Further studies will show whether these interactions are involved in HSV-induced immune suppression.
树突状细胞（DCs）对于诱导针对入侵病原体的特异性免疫反应至关重要。单纯疱疹病毒（HSV）是一种常见的人类病原体，可引起皮肤和黏膜的疼痛但轻微感染，并导致潜伏和复发性感染。在已描述的两种HSV亚型中，HSV-1主要引起口腔面部病变，而HSV-2与生殖器疱疹有关。DCs参与HSV诱导的免疫抑制，但关于DCs与HSV之间的分子相互作用知之甚少。本研究表明，HSV-1和-2均与DC特异性C型凝集素DC-SIGN相互作用。进一步分析表明，DC-SIGN与HSV糖蛋白gB和gC相互作用。HSV-1与未成熟DCs的结合依赖于DC-SIGN和硫酸乙酰肝素蛋白聚糖。引人注目的是，针对DC-SIGN的阻断抗体几乎完全抑制了DCs的HSV-1感染。因此，DC-SIGN是未成熟DCs上HSV-1的重要附着受体，并在顺式中增强DCs的感染。此外，DC-SIGN捕获HSV-1以传递给允许性靶细胞。这些数据强烈表明，DC-SIGN是预防HSV感染和病毒传播的潜在靶点。进一步的研究将表明这些相互作用是否参与HSV诱导的免疫抑制。
