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J. Virol. doi:10.1128/JVI.01419-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Region Between the Canine Distemper Virus M and F Genes Modulates Virulence by Controlling Fusion Protein Expression

INRS-Institut Armand-Frappier, University of Quebec, Laval, Quebec, Canada

^* To whom correspondence should be addressed. Email: veronika.vonmessling{at}iaf.inrs.ca.

	Abstract

Morbilliviruses, including measles and canine distemper virus (CDV), are non-segmented, negative-strand RNA viruses that cause severe disease in humans and animals. The transcriptional units in their genome are separated by untranslated regions (UTRs), which contain essential transcription and translation signals. Due to its increased length, the region between the matrix (M) and fusion (F) protein open reading frames is of particular interest. In measles, the entire F 5' region is untranslated, while several start codons are found in most other morbilliviruses, resulting in a long F protein signal peptide (Fsp). To characterize the role of this region in morbillivirus pathogenesis, we constructed recombinant CDVs, in which either the M-F UTR was replaced with that between the nucleocapsid (N) and phosphoprotein (P) genes or 106 Fsp residues were deleted. The Fsp deletion alone had no effect in vitro and in vivo. In contrast, substitution of the UTR was associated with a slight increase in F gene and protein expression. Animals infected with this virus either recovered completely or experienced a prolonged disease and death due to neuroinvasion. The combination of both changes resulted in a virus with strongly increased F gene and protein expression and complete attenuation. Taken together, our results provide evidence that the region between the morbillivirus M and F genes modulates virulence through transcriptional control of F gene expression.