Affordable Access

deepdyve-link
Publisher Website

Region between the canine distemper virus M and F genes modulates virulence by controlling fusion protein expression.

Authors
  • Anderson, Danielle E
  • von Messling, Veronika
Type
Published Article
Journal
Journal of Virology
Publisher
American Society for Microbiology
Publication Date
Nov 01, 2008
Volume
82
Issue
21
Pages
10510–10518
Identifiers
DOI: 10.1128/JVI.01419-08
PMID: 18753197
Source
Medline
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times