Spielhofer P, Bächi T, Fehr T, Christiansen G, Cattaneo R, Kaelin K, Billeter M A, Naim H Y
Institute of Molecular Biology Division I, University of Zürich, Switzerland.
J Virol. 1998 Mar;72(3):2150-9. doi: 10.1128/JVI.72.3.2150-2159.1998.
Measles virus (MV) and vesicular stomatitis virus (VSV) are both members of the Mononegavirales but are only distantly related. We generated two genetically stable chimeric viruses. In MGV, the reading frames of the MV envelope glycoproteins H and F were substituted by a single reading frame encoding the VSV G glycoprotein; MG/FV is similar but encodes a G/F hybrid in which the VSV G cytoplasmic tail was replaced by that of MV F. In contrast to MG/FV, MGV virions do not contain the MV matrix (M) protein. This demonstrates that virus assembly is possible in the absence of M; conversely, the cytoplasmic domain of F allows incorporation of M and enhances assembly. The formation of chimeric viruses was substantially delayed and the titers obtained were reduced about 50-fold in comparison to standard MV. In the novel chimeras, transcription and replication are mediated by the MV ribonucleoproteins but the envelope glycoproteins dictate the host range. Mice immunized with the chimeric viruses were protected against lethal doses of wild-type VSV. These findings suggest that it is feasible to construct MV variants bearing a variety of different envelopes for use as vaccines or for gene therapeutic purposes.
麻疹病毒（MV）和水疱性口炎病毒（VSV）均为单股负链RNA病毒目成员，但亲缘关系甚远。我们构建了两种基因稳定的嵌合病毒。在MGV中，MV包膜糖蛋白H和F的读码框被编码VSV G糖蛋白的单一读码框取代；MG/FV与之相似，但编码一种G/F杂种蛋白，其中VSV G的胞质尾被MV F的胞质尾取代。与MG/FV不同，MGV病毒粒子不含MV基质（M）蛋白。这表明在没有M蛋白的情况下病毒组装是可能的；相反，F蛋白的胞质结构域允许M蛋白掺入并增强组装。与标准MV相比，嵌合病毒的形成显著延迟，获得的滴度降低了约50倍。在新型嵌合体中，转录和复制由MV核糖核蛋白介导，但包膜糖蛋白决定宿主范围。用嵌合病毒免疫的小鼠对致死剂量的野生型VSV具有抵抗力。这些发现表明构建携带多种不同包膜的MV变体用作疫苗或用于基因治疗目的是可行的。
