Evaluation of the Contributions of Individual Viral Genes to Newcastle Disease Virus Virulence and Pathogenesis

Paldurai, Anandan; Kim, Shin-Hee; Nayak, Baibaswata; Xiao, Sa; Shive, Heather R.; Collins, Peter L.; Samal, Siba K.

doi:10.1128/jvi.00666-14

Cited by 54 publications

(44 citation statements)

References 26 publications

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“…Presumably the same could play an important role in the P gene of NDV in modulating its pathotypes. It has been shown that P gene also modulates the pathogenicity of NDV in chicken . However, the study requires an in depth analysis of NDV pathogenesis by codon optimized P gene using reverse genetics.…”

Section: Discussionmentioning

confidence: 99%

Synonymous codon usage of genes in polymerase complex of Newcastle disease virus

Kumar

2017

J Basic Microbiol

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Newcastle disease virus (NDV) is pathogenic to both avian and non-avian species but extensively finds poultry as its primary host and causes heavy economic losses in the poultry industry. In this study, a total of 186 polymerase complex comprising of nucleoprotein (N), phosphoprotein (P), and large polymerase (L) genes of NDV was analyzed for synonymous codon usage. The relative synonymous codon usage and effective number of codons (ENC) values were used to estimate codon usage variation in each gene. Correspondence analysis (COA) was used to study the major trend in codon usage variation. Analyzing the ENC plot values against GC3s (at synonymous third codon position) we concluded that mutational pressure was the main factor determining codon usage bias than translational selection in NDV N, P, and L genes. Moreover, correlation analysis indicated, that aromaticity of N, P, and L genes also influenced the codon usage variation. The varied distribution of pathotypes for N, P, and L gene clearly suggests that change in codon usage for NDV is pathotype specific. The codon usage preference similarity in N, P, and L gene might be detrimental for polymerase complex functioning. The study represents a comprehensive analysis to date of N, P, and L genes codon usage pattern of NDV and provides a basic understanding of the mechanisms for codon usage bias.

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Section: Discussionmentioning

confidence: 99%

Synonymous codon usage of genes in polymerase complex of Newcastle disease virus

Kumar

2017

J Basic Microbiol

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“…A number of studies have shown that while the F protein is critical in predicting the behavior of an NDV, pathogenicity is multifactorial and proteins other than the F protein may play key roles. 11,22,28 There have been limited in vivo experimental studies using Australian NDV isolates. Previous experimental studies using an Australian virus with a virulent F protein cleavage site of 112 RRQRRF 117 , isolated from Glenorie, NSW (9809-19-1107), found that affected birds showed mild to severe depression, respiratory disease, and neurological signs with no mortalities and recovery after 10 days.…”

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confidence: 99%

An Australian Newcastle Disease Virus With a Virulent Fusion Protein Cleavage Site Produces Minimal Pathogenicity in Chickens

et al. 2017

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Newcastle disease is an important disease of poultry caused by virulent strains of Newcastle disease virus (NDV). During the 1998 to 2002 outbreaks of Newcastle disease in Australia, it was observed that the mild clinical signs seen in some chickens infected with NDV did not correlate with the viruses' virulent fusion protein cleavage site motifs or standard pathogenicity indices. The pathogenicity of 2 Australian NDV isolates was evaluated in experimentally challenged chickens based on clinical evaluation, histopathology, immunohistochemistry, and molecular techniques. One of these virus isolates, Meredith/02, was shown to induce only very mild clinical signs with no mortalities in an experimental setting, in contrast to the velogenic Herts 33/56 and Texas GB isolates. This minimal pathogenicity was associated with decreased virus replication and antigen distribution in tissues. This demonstrates that the Australian Meredith/02 NDV, despite possessing a virulent fusion protein cleavage site, did not display a velogenic phenotype.

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“…Studies using reverse genetics have also indicated that regions of the NDV genome other than the F protein cleavage site may also contribute significantly to pathogenicity. 3,12,120 For example, the viral replication complex has been associated with the decreased pathogenicity of the pigeon paramyxovirus for chickens, despite its virulent cleavage site motif. 12 Overall, this experimental work has confirmed the field observations, that despite containing a virulent F protein cleavage site as defined by the OIE, the Meredith/02 isolate of NDV is not highly pathogenic for chickens.…”

Section: Discussionmentioning

confidence: 99%

“…This was associated with 3 amino acid mutations, 2 in the L protein and 1 in the P. 148 A further study examining all 6 NDV genes showed that whilst the F gene is the main determinant of pathogenicity, the polymerase L gene is the second most important contributor. 120 …”

Section: Viral Replication Complexmentioning

confidence: 99%

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The molecular basis of the pathogenicity of Newcastle disease virus in chickens

Bergfeld¹

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Newcastle disease (ND) is a highly pathogenic disease of poultry and is caused by virulent strains of Newcastle disease virus (NDV). From 1998From -2002 there were outbreaks of ND in Australia which resulted in significant disruptions to the poultry industry. In some of these outbreaks however, the clinical signs observed in the infected birds did not appear to correlate with the World Organisation for Animal Health's definition of a virulent virus, which is based on the molecular sequence at the fusion protein cleavage site. In one particular outbreak at Meredith, Victoria, in 2002, a virulent virus was isolated, despite only a minimal increase in mortalities on the property. Therefore, this thesis has attempted to determine whether, in addition to the fusion protein cleavage site, there are other molecular determinants of pathogenicity for NDV. NDV. Sequence analysis showed a number of amino acid differences throughout the genomes of the four viruses studied, however none of these differences were in key areas such as glycosylation sites. The Meredith/02 virus was also shown to replicate well in embryonated eggs, throughout the chorioallantoic membrane and internal organs of the embryo, including the lung, liver and kidneys. This is consistent with other virulent NDVs.ii The V protein of the Meredith/02 virus was investigated for its role in potential attenuation of the virus via modulation of the host innate immune response. However there was no difference found in the ability of the Meredith/02 V protein to antagonise type I interferon in-vitro when compared with the Herts 33/56 virus.In an attempt to analyse the viral replication complex, to identify a specific protein that may be involved with the minimal pathogenicity of the Meredith/02 virus, the transcription gradient of the virus was characterized. It was found that the Meredith/02 virus has an increased transcription gradient when compared with the Herts 33/56 virus. The gradient of the Meredith/02 virus was particularly steep at the N-P junction, with particularly low levels of the P gene transcribed at 24 hours. However, gene start and end sequences at this location did not vary between the two viruses, thereby indicating that the N and P proteins are less likely to be associated with the steepened gradient. Instead, this suggests a possible role for the large polymerase protein in decreasing transcription.Whilst this research has not yet identified specific molecular sequences responsible for the minimal pathogenicity of the Meredith/02 virus despite its virulent fusion protein cleavage site, it has focused the investigation on components of the viral replication complex.Therefore directions for further research include investigating the role of the replication complex, in particular, the large polymerase (L) gene in the pathogenicity of Australian NDVs. This could also incorporate further work on the individual proteins via the use of minigenome assays, or by utilising reverse genetics and full-length virus clones.

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Evaluation of the Contributions of Individual Viral Genes to Newcastle Disease Virus Virulence and Pathogenesis

Cited by 54 publications

References 26 publications

Synonymous codon usage of genes in polymerase complex of Newcastle disease virus

Synonymous codon usage of genes in polymerase complex of Newcastle disease virus

An Australian Newcastle Disease Virus With a Virulent Fusion Protein Cleavage Site Produces Minimal Pathogenicity in Chickens

The molecular basis of the pathogenicity of Newcastle disease virus in chickens

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