Singethan K, Topfstedt E, Schubert S, Duprex W P, Rima B K, Schneider-Schaulies Jürgen
Institut für Virologie und Immunbiologie, Versbacher Straße 7, D-97078 Würzburg, Germany.
School of Biomedical Sciences, The Queen's University of Belfast, Belfast BT9 7BL, UK.
J Gen Virol. 2006 Jun;87(Pt 6):1635-1642. doi: 10.1099/vir.0.81629-0.
Antibodies to CD9, a member of the tetraspan transmembrane-protein family, selectively inhibit Canine distemper virus (CDV)-induced cell-cell fusion. Neither CDV-induced virus-cell fusion nor cell-cell fusion induced by the closely related morbillivirus Measles virus (MV) is affected by anti-CD9 antibodies. As CDV does not bind CD9, an unknown, indirect mechanism is responsible for the observed inhibition of cell-cell fusion. It was investigated whether this effect was restricted to only one viral glycoprotein, either the haemagglutinin (H) or the fusion (F) protein, which form a fusion complex on the surface of virions and infected cells, or whether it is dependent on both in transient co-transfection assays. The susceptibility to CD9 antibodies segregates with the H protein of CDV. By exchanging portions of the H proteins of CDV and MV, it was determined that the complete extracellular domain, including the predicted stem structure (stem 1, barrel strand 1 and stem 2) and globular head domain, of the CDV-H protein mediates the effect. This suggests that interaction of the CDV-H protein with an unknown cellular receptor(s) is regulated by CD9, rather than F protein-mediated membrane fusion.
CD9是四跨膜蛋白家族的成员之一，针对CD9的抗体可选择性抑制犬瘟热病毒（CDV）诱导的细胞-细胞融合。抗CD9抗体对CDV诱导的病毒-细胞融合以及密切相关的麻疹病毒（MV）诱导的细胞-细胞融合均无影响。由于CDV不与CD9结合，因此观察到的细胞-细胞融合抑制作用是由一种未知的间接机制导致的。研究了这种效应是否仅局限于病毒粒子和受感染细胞表面形成融合复合物的两种病毒糖蛋白之一，即血凝素（H）蛋白或融合（F）蛋白，还是在瞬时共转染试验中依赖于两者。对CD9抗体的敏感性与CDV的H蛋白相关。通过交换CDV和MV的H蛋白部分，确定CDV-H蛋白的完整胞外结构域，包括预测的茎结构（茎1、桶状链1和茎2）和球状头部结构域，介导了这种效应。这表明CDV-H蛋白与未知细胞受体的相互作用受CD9调控，而非F蛋白介导的膜融合。
