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Newcastle Disease Virus | 49

responses by induction of type I interferon (IFN) (Fournier et al., P gene mRNA editing
2012; Oh et al., 2016). Like all other members of Paramyxoviridae, NDV increases the
The polymerase then transcribes the genes sequentially in coding capacity of its P gene by RNA editing (Lamb and Parks,
their 3′ to 5′ order to yield individual mRNAs by a start-stop- 2013). Editing of P mRNA occurs when the RdRp responds to a
restart mechanism guided by the conserved GS and GE signals. cis-acting sequence 3′-UUUUUCCC-5′ at position 484 in the P
GS initiates synthesis of the mRNA and GE directs polyadenyla- gene ORF, causing stuttering of cytosine residues (Steward et al.,
tion and termination of the mRNA, after which the polymerase 1993). The insertion of extra G residues at the editing site results
remains attached to the template and passes over the IGS to in a frameshift when the mRNA is translated, giving rise to dif-
locate the next GS signal. Therefore, the IGSs are not copied into ferent proteins depending on how many G residues were added:
mRNAs. The RdRp moves along the nucleocapsid presumably by The P protein (no insertion), the V protein (one G insertion) or
displacing and replacing the N subunits. The mRNAs are capped, the W protein (two G insertion). Thus, as shown in Fig. 2.5, the
methylated and polyadenylated by the viral polymerase. However, P, V and W proteins are amino coterminal, but they vary at their
unlike eukaryotic mRNAs, NDV mRNAs are not methylated at carboxyl termini, both in length and in aa composition. Analysis
the penultimate residue (Colonno and Stone, 1976). The poly of mRNAs produced from the P gene showed that 68% were
(A) tail is synthesized by stuttering on the stretch of U residues in P-encoding mRNAs, 29% were V-encoding mRNAs, and 2%
the GE signal. Following polyadenylation, the mRNA is released were W-encoding mRNAs (Mebatsion et al., 2001). An in vitro
from the polymerase by an unknown mechanism. Occasional dis- study showed that the ratio of P:V:W transcripts varied slightly
sociation of the polymerase from the template occurs, which leads with the strain of NDV and with time of infection (Qiu et al.,
to a gradient of mRNA abundance that decreases according to the 2016a).
distance from the 3′-end of the genome. The gradient transcrip-
tion does not seem to be arbitrary in that the gene whose product RNA replication
is required in large amount (e.g. N protein) is located at the 3′-end The replication of the genome occurs when the polymerase ini-
and the gene whose product is needed in small amount (e.g. L tiates RNA synthesis at the first nt at the 3′-end of the genome
protein) is located at the 5′-end. This is a mechanism by which and ignores the GS and GE signals, producing a complete, exact
non-segmented, negative-strand RNA viruses express different positive-sense copy of the genome called the antigenome (Fig.
genes at different levels. Sometimes read-through transcription 2.4). The 3′-end of the antigenome contains the complement
can occur, when the polymerase fails to terminate at GE resulting of the trailer, known as antigenome promoter. The antigenome
in a polycistronic mRNA, of which only the upstream cistron is promoter then signals the polymerase to synthesize progeny
translated. The NDV genome is used with great efficiency, as over genomes using the antigenome as template. The anitgenomes
95% of the RNA encode viral proteins. and genomes are not capped but are encapsidated with N pro-
Each NDV mRNA contains a major ORF with short 5′ tein. Concomitant with viral RNA synthesis, the monomers of N
0
0
and 3′ untranslated regions (UTRs). The UTRs exert another protein (N ) associates with P protein to form a soluble (N –P)
level of transcription control, ultimately affecting the level of complex, which is delivered to the elongating RNA for encapsi-
translated proteins. The sequence and length of the UTRs vary dation. The genomic RNAs are used as templates for secondary
among the different mRNA species. It has been shown that the transcription, for incorporation into newly formed virus parti-
5′ UTR modulates the level of transcription and translation of cles and to serve as template for antigenome synthesis, whereas
downstream gene and affects virus replication and pathogenic- antigenomic RNAs are only used as template for synthesis of
ity (Yan et al., 2009). The effect of 3′ UTR in transcription and genomic RNA. It has been shown that the antigenome promoter
translation is not well known but may play a role in translation is stronger than the genome promoter, resulting in synthesis of
of the mRNA. more genome sense RNAs (Keller and Parks, 2003). The transi-
Initiation of transcription occurs immediately after delivery tion from positive to negative-sense RNA synthesis occurs at a
of the RNP core into the cytoplasm. The initial period of tran- late stage of infection, because more genome sense nucleocapsids
scription is called primary transcription when large amounts are needed for packaging into virus particles. It has been shown in
of viral mRNAs are produced from the input nucleocapsid. At other paramyxoviruses that this transition occurs by the action of
some point after primary transcription the polymerase switches a trans-acting protein (Irie et al., 2008). Although, the trans-acting
to a replication mode to synthesize full length complemen- protein involved in switching of NDV transcription is not known,
tary strand of the genome. The switch from transcription to one possible candidate is the V protein. The V protein is a mul-
replication is postulated to be controlled by the intracellular tifunctional protein, which can bind to the polymerase complex
concentration of the N protein. When the concentration of N and can cause this transition.
protein is high enough to allow encapsidation of the nascent
RNA chain, the replication mode of the polymerase is favoured
over transcription mode (Horikami et al., 1992; Baker and Viral proteins
Moyer, 1998). The occurrence of switch from transcription to The genome of NDV encodes eight proteins: N, P, V/W, M, F,
replication is not fully clear, but it may involve participation of HN and L. However, not much is known about the W protein.
host factors. Secondary transcription occurs when mRNAs are The remaining seven proteins are found in virus particles. Three
synthesized from newly formed genomic RNAs. proteins (N, P and L), together with the RNA genome form the