Page 55 - Avian Virology: Current Research and Future Trends

48 | Samal

The beginning and end of each gene contain conserved NDV (Yan and Samal, 2008). Therefore, IGS play an important
transcriptional control sequences known as the gene-start (GS) role in controlling the transcription level of each gene. The
(3′-UGCCCAUCU/CU-5′) and gene-end (GE) (3′-AAUU/ sequence of IGS vary among NDV strains, indicating that the
CC/UU -5′), respectively (Fig. 2.3B). The GS and GE sequence of IGS is probably not important for modulation of
5–6
sequences are not required for RNA replication. Between the NDV transcription.
gene boundaries are non-coding intergenic sequences (IGSs),
which vary in length from 1 to 47 nt. Each of the first three Transcription
IGSs, the N-P, P-M, and M-F gene junctions, has only 1 nt, NDV transcription follows the general model of the order Mon-
while the other two IGSs, the F-HN and HN-L gene junctions onegavirales (Lamb, 2013). The viral RdRp complex contains the
are 31 nt and 47 nt, respectively. The lengths of IGSs are gener- L protein which has the enzymatic domains involved in RNA
ally conserved among NDV strains, with the exception that synthesis, capping and methylation and the P protein, which is
the IGS in the N-P gene junction is 2 nt long in some strains; an essential cofactor. The RdRp enters the genome at a single pro-
examples, LaSota, D26 and Texas GB. It has been shown that moter located in the leader region (Fig. 2.4). A small leader RNA
the IGS length modulates the transcription of the downstream is first transcribed from the first 55 nt of the genome (Kurilla et al.,
gene (Kim and Samal, 2010). The length of IGS at each gene 1985). The leader RNA has 5′-triphosphate and is not capped or
junction is conserved evolutionarily, because only these lengths polyadenylated. The role of the leader RNA in viral replication is
probably produce the optimal amounts of transcripts necessary not completely known. However, recognition of uncapped leader
for efficient NDV replication. Any increase or decrease of the RNA in the cytoplasm of NDV infected cells by retinoic acid-
natural IGS length affects the replication and pathogenicity of inducible gene-I (RIG-I) has been reported to initiate antiviral

N P M F HN L
protein protein protein protein protein protein

C An Translation
C An C An
C An C An C An
C An C An C An C An
C An C An C An C An C An
C An C An C An C An C An C An
Le N P M F HN L
mRNA mRNA mRNA mRNA mRNA mRNA

Pol Transcription

3’ 5’

Genome (-) strand

Replication
Pol

5’ 3’
Antigenome (+) strand

Figure 2.4 Transcription and replication of Newcastle disease virus. The negative-sense genomic RNA encapsidated by the N protein
serves as a template for the polymerase complex (L protein associated with the P protein). Transcription starts with a short uncapped,
non-polyadenylated leader RNA (Le) from the 3′ end of the genomic RNA; this is followed by the transcription of 5′ capped and polyadenylated
mRNAs, which are translated into proteins. During transcription, the polymerase complex stops at gene-end (GE) sequence and restarts at
the next gene-start (GS) sequence, but the restart attempts are not always successful; therefore, attenuation of transcription occurs in the
direction of 3′–5′ (transcription gradient). During replication, the polymerase complex ignores GS and GE signals, rendering a full-length
antigenomic (+) RNA, which is also encapsidated by N protein. The antigenomic RNA then serves as a template for synthesis of additional
copies of genomic (–) RNA.