Chimeric measles viruses with a foreign envelope.
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.
Spielhofer
P
P
Institute of Molecular Biology Division I, University of Zürich, Switzerland.
Bächi
T
T
Fehr
T
T
Christiansen
G
G
Cattaneo
R
R
Kaelin
K
K
Billeter
M A
MA
Naim
H Y
HY
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D010957:Plasmids; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014771:Virion / Q000648:ultrastructure; D019065:Virus Assembly
C028391:G protein, vesicular stomatitis virus; D006389:Hemagglutinins, Viral; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C032397:hemagglutinin protein G, measles virus