Van de Walle Gerlinde R, Peters Sarah T, VanderVen Brian C, O'Callaghan Dennis J, Osterrieder Nikolaus
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Virol. 2008 Dec;82(23):11859-68. doi: 10.1128/JVI.00868-08. Epub 2008 Sep 24.
Equine herpesvirus 1 (EHV-1) is a member of the Alphaherpesvirinae, and its broad tissue tropism suggests that EHV-1 may use multiple receptors to initiate virus entry. EHV-1 entry was thought to occur exclusively through fusion at the plasma membrane, but recently entry via the endocytic/phagocytic pathway was reported for Chinese hamster ovary cells (CHO-K1 cells). Here we show that cellular integrins, and more specifically those recognizing RGD motifs such as alphaVbeta5, are important during the early steps of EHV-1 entry via endocytosis in CHO-K1 cells. Moreover, mutational analysis revealed that an RSD motif in the EHV-1 envelope glycoprotein D (gD) is critical for entry via endocytosis. In addition, we show that EHV-1 enters peripheral blood mononuclear cells predominantly via the endocytic pathway, whereas in equine endothelial cells entry occurs mainly via fusion at the plasma membrane. Taken together, the data in this study provide evidence that EHV-1 entry via endocytosis is triggered by the interaction between cellular integrins and the RSD motif present in gD and, moreover, that EHV-1 uses different cellular entry pathways to infect important target cell populations of its natural host.
马疱疹病毒1型（EHV-1）是α疱疹病毒亚科的成员，其广泛的组织嗜性表明EHV-1可能利用多种受体启动病毒进入。EHV-1的进入曾被认为仅通过在质膜处融合发生，但最近有报道称中国仓鼠卵巢细胞（CHO-K1细胞）可通过内吞/吞噬途径进入。在此我们表明，细胞整合素，更具体地说是那些识别RGD基序（如αVβ5）的整合素，在CHO-K1细胞中EHV-1通过内吞作用进入的早期步骤中很重要。此外，突变分析表明EHV-1包膜糖蛋白D（gD）中的一个RSD基序对于通过内吞作用进入至关重要。此外，我们表明EHV-1主要通过内吞途径进入外周血单核细胞，而在马内皮细胞中，进入主要通过在质膜处融合发生。综上所述，本研究中的数据提供了证据，表明细胞整合素与gD中存在的RSD基序之间的相互作用触发了EHV-1通过内吞作用进入，而且EHV-1利用不同的细胞进入途径感染其天然宿主的重要靶细胞群体。
