Role of Intergenic Sequences in Newcastle Disease Virus RNA Transcription and Pathogenesis

Ebola virus (EBOV) belongs IMPORTANCEOur current understanding of EBOV transcription regulation is limited due to the requirement for high-containment conditions to study this highly pathogenic virus. EBOV is thought to share many mechanistic features with well-analyzed prototype nonsegmented negative-sense RNA viruses. A single polymerase entry site at the 3= end of the genome determines that transcription of the genes is mainly controlled by gene order and cis-acting signals found at the gene borders. Here, we examined the regulatory role of the structurally unique EBOV gene borders during viral transcription. Our data suggest that transcriptional regulation in EBOV is highly complex and differs from that in prototype viruses and further the understanding of this most fundamental process in the filovirus replication cycle. Moreover, our results with recombinant EBOVs suggest a novel role of the long IR found in all filovirus genomes during the viral replication cycle.

Section: Discussionsupporting

confidence: 74%

Analysis of the Highly Diverse Gene Borders in Ebola Virus Reveals a Distinct Mechanism of Transcriptional Regulation

Brauburger

Boehmann

Tsuda

et al. 2014

“…Critical sequences for polyadenylation, located in the last seven nucleotides of the simian virus 5 M 3Ј UTR, increase readthrough by the vRdRp during transcription at the M-F gene junction, thereby lowering the level of F protein produced while increasing the transcription of downstream genes (23). However, a recent study with Newcastle disease virus demonstrates that the nonspecific expansion of a UTR results in reduced transcription of the downstream gene, suggesting that specific regulatory elements may not be needed to modulate transcription (36). In the case of MeV, it has been shown that the M 3Ј UTR promotes viral replication by increasing the M protein production, while the F 5Ј UTR decreases replication and reduces the F protein production and cytopathogenicity (28) (30).…”

Section: Discussionmentioning

confidence: 94%

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

Anderson

Messling

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.

“…NDV has a nonsegmented, negative-sense RNA genome consisting of six transcriptional units (3=-NP-P-M-F-HN-L-5=) (4,8). NDV strains have been classified into classes I (9 genotypes) and II (11 genotypes): class I strains are generally avirulent and have been isolated mainly from wild birds, whereas class II strains are virulent and avirulent and have been isolated from wild and domestic birds (2,6).…”

mentioning

confidence: 99%

Complete Genome Sequence Analysis of a Newcastle Disease Virus Isolated from a Wild Egret

Xie

Chen

et al. 2012

We report here the complete genomic sequence of a novel Newcastle disease virus (NDV) strain, egret/China/Guangxi/ 2011, isolated from an egret in Guangxi Province, southern China. A phylogenetic analysis based on a fusion gene comparison with different NDV strains revealed that egret/China/Guangxi/2011 was phylogenetically close to genotype VIIa NDV, and the deduced amino acid sequence was 112 R-R-R-K-R-F 117 at the fusion protein cleavage site. The whole nucleotide sequence had the highest homology (93.3%) with the sequence of strain chicken/Sukorejo/019/10 (GenBank accession number HQ697255). This study will help us to understand the epidemiology and molecular characteristics of Newcastle disease virus in a migratory egret.