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Journal of Virology, November 2008, p. 10510-10518, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01419-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Region between the Canine Distemper Virus M and F Genes Modulates Virulence by Controlling Fusion Protein Expression{triangledown}

Danielle E. Anderson{dagger} and Veronika von Messling*

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

Received 8 July 2008/ Accepted 19 August 2008

Morbilliviruses, including measles and canine distemper virus (CDV), are nonsegmented, negative-stranded RNA viruses that cause severe diseases in humans and animals. The transcriptional units in their genomes are separated by untranslated regions (UTRs), which contain essential transcription and translation signals. Due to its increased length, the region between the matrix (M) protein and fusion (F) protein open reading frames is of particular interest. In measles virus, 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 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 the F gene expression.


* Corresponding author. Mailing address: INRS-Institut Armand-Frappier, University of Quebec, 531 Boul. des Prairies, Laval, Quebec H7V 1B7, Canada. Phone: (450) 687-5010. Fax: (450) 686-5309. E-mail: veronika.vonmessling{at}iaf.inrs.ca

{triangledown} Published ahead of print on 27 August 2008.

{dagger} Danielle E. Anderson's maiden name is Magoffin.


Journal of Virology, November 2008, p. 10510-10518, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01419-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.