Nussbaum O, Broder C C, Moss B, Stern L B, Rozenblatt S, Berger E A
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
J Virol. 1995 Jun;69(6):3341-9. doi: 10.1128/JVI.69.6.3341-3349.1995.
We analyzed the roles of the individual measles virus (MV) surface glycoproteins in mediating functional and structural interactions with human CD46, the primary MV receptor. On one cell population, recombinant vaccinia virus vectors were used to produce the MV hemagglutinin (H) and fusion (F) glycoproteins. As fusion partner cells, various cell types were examined, without or with human CD46 (endogenous or recombinant vaccinia virus encoded). Fusion between the two cell populations was monitored by a quantitative reporter gene activation assay and by syncytium formation. MV glycoproteins promoted fusion with primate cells but not with nonprimate cells; recombinant CD46 rendered nonprimate cells competent for MV glycoprotein-mediated fusion. Markedly different fusion specificity was observed for another morbillivirus, canine distemper virus (CDV): recombinant CDV glycoproteins promoted fusion with primate and nonprimate cells independently of CD46. Fusion by the recombinant MV and CDV glycoproteins required coexpression of H plus F in either homologous or heterologous combinations. To assess the role of H versus F in determining the CD46 dependence of MV fusion, we examined the fusion specificities of cells producing heterologous glycoprotein combinations. The specificity of HMV plus FCDV paralleled that observed for the homologous MV glycoproteins: fusion occurred with primate cells but not with nonprimate cells unless they produced recombinant CD46. By contrast, the specificity of HCDV plus FMV paralleled that for the homologous CDV glycoproteins: fusion occurred with either primate or nonprimate cells with no dependence on CD46. Thus, for both MV and CDV, fusion specificity was determined by H. In particular, the results demonstrate a functional interaction between HMV and CD46. Flow cytometry and antibody coprecipitation studies provided a structural correlate to this functional interaction: CD46 formed a molecular complex with HMV but not with FMV or with either CDV glycoprotein. These results highlight the critical role of the H glycoprotein in determining MV specificity for CD46-positive cells.
我们分析了麻疹病毒（MV）各表面糖蛋白在介导与人类CD46（主要的MV受体）的功能和结构相互作用中的作用。在一个细胞群体上，利用重组痘苗病毒载体产生MV血凝素（H）和融合（F）糖蛋白。作为融合伙伴细胞，我们检测了各种细胞类型，这些细胞有无人类CD46（内源性或重组痘苗病毒编码的）。通过定量报告基因激活试验和多核体形成来监测两个细胞群体之间的融合。MV糖蛋白促进与灵长类细胞的融合，但不促进与非灵长类细胞的融合；重组CD46使非灵长类细胞具备MV糖蛋白介导的融合能力。对于另一种麻疹病毒——犬瘟热病毒（CDV），观察到明显不同的融合特异性：重组CDV糖蛋白促进与灵长类和非灵长类细胞的融合，且不依赖于CD46。重组MV和CDV糖蛋白的融合需要H和F以同源或异源组合的方式共表达。为了评估H与F在确定MV融合对CD46的依赖性中的作用，我们检测了产生异源糖蛋白组合的细胞的融合特异性。HMV加FCDV的特异性与同源MV糖蛋白观察到的特异性相似：与灵长类细胞发生融合，但不与非灵长类细胞融合，除非它们产生重组CD46。相比之下，HCDV加FMV的特异性与同源CDV糖蛋白的特异性相似：与灵长类或非灵长类细胞都发生融合，且不依赖于CD46。因此，对于MV和CDV，融合特异性均由H决定。特别是，结果证明了HMV与CD46之间的功能相互作用。流式细胞术和抗体共沉淀研究为这种功能相互作用提供了结构关联：CD46与HMV形成分子复合物，但不与FMV或任何一种CDV糖蛋白形成复合物。这些结果突出了H糖蛋白在确定MV对CD46阳性细胞的特异性中的关键作用。
