CHIMERIC MEASLES VIRUSES WITH A FOREIGN ENVELOPE

Measles virus (MV) and vesicular stomatitis virus (VSV) are both membe rs of the Monoegavirales but are only distantly related, We generated two genetically stable chimeric viruses. In MGV, the reading frames of the MC envelope glycoproteins H and F were substituted by a single re ading frame encoding the VSV G glycoprotein; MG/FV is similar but enco des a GIF hybrid in which the VSV G cytoplasmic tail was replaced by t hat of MV F. In contrast to MG/FV, MGV virions do not contain the MV m atrix (M) protein. This demonstrates that virus assembly is possible i n the absence of hi; conversely, the cytoplasmic domain of F allows in corporation of hi and enhances assembly. The formation of chimeric vir uses was substantially delayed and the titers obtained were reduced ab out 50-fold in comparison to standard MV. In the novel chimeras, trans cription and replication are mediated by the MV ribonucleoproteins but the envelope glycoproteins dictate the host range. Mice immunized wit h the chimeric viruses were protected against lethal doses of wild-typ e VSV. These findings suggest that it is feasible to construct MV vari ants hearing a variety of different envelopes for use as vaccines or f or gene therapeutic purposes.