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J Virol, March 1998, p. 2150-2159, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Chimeric Measles Viruses with a Foreign Envelope

Pius Spielhofer,1 Thomas Bächi,2 Thomas Fehr,3 Gudrun Christiansen,1 Roberto Cattaneo,1 Karin Kaelin,1 Martin A. Billeter,1 and Hussein Y. Naim1,*

Institute of Molecular Biology Division I1 and Institute for Experimental Immunology, Department of Pathology,3 University of Zürich, and Elekronenmikroskopisches Zentrallaboratorium,2 Zürich, Switzerland

Received 18 September 1997/Accepted 14 November 1997

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.

* Corresponding author. Mailing address: Institut für Molekularbiologie, Abteilung I, Universität Zürich, Hönggerberg, CH-8093 Zürich, Switzerland. Phone: 41 (1) 633 24 94. Fax: 41 (1) 371 72 05. E-mail: naim{at}molbio1.unizh.ch.




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