Complete genome sequence of highly virulent neurotropic Newcastle disease virus strain Texas GB

Paldurai, Anandan; Kumar, Sachin; Nayak, Baibaswata; Samal, Siba K.

doi:10.1007/s11262-010-0486-3

Cited by 20 publications

(14 citation statements)

References 27 publications

(30 reference statements)

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“…In The NDV fusion protein CT is 31 amino acids long (amino acid positions 523 to 553) ( Fig. 1) and is highly conserved among different strains of NDV (20,(45)(46)(47). It has been previously reported that deletions in the NDV F CT greatly reduced syncytium formation (48).…”

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confidence: 94%

Mutations in the Cytoplasmic Domain of the Newcastle Disease Virus Fusion Protein Confer Hyperfusogenic Phenotypes Modulating Viral Replication and Pathogenicity

Samal

Khattar

Paldurai

et al. 2013

J Virol

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bThe Newcastle disease virus (NDV) fusion protein (F) mediates fusion of viral and host cell membranes and is a major determinant of NDV pathogenicity. In the present study, we demonstrate the effects of functional properties of F cytoplasmic tail (CT) amino acids on virus replication and pathogenesis. Out of a series of C-terminal deletions in the CT, we were able to rescue mutant viruses lacking two or four residues (r⌬2 and r⌬4). We further rescued viral mutants with individual amino acid substitutions at each of these four terminal residues (rM553A, rK552A, rT551A, and rT550A). In addition, the NDV F CT has two conserved tyrosine residues (Y524 and Y527) and a dileucine motif (LL536-537). In other paramyxoviruses, these residues were shown to affect fusion activity and are central elements in basolateral targeting. The deletion of 2 and 4 CT amino acids and single tyrosine substitution resulted in hyperfusogenic phenotypes and increased viral replication and pathogenesis. We further found that in rY524A and rY527A viruses, disruption of the targeting signals did not reduce the expression on the apical or basolateral surface in polarized Madin-Darby canine kidney cells, whereas in double tyrosine mutant, it was reduced on both the apical and basolateral surfaces. Interestingly, in rL536A and rL537A mutants, the F protein expression was more on the apical than on the basolateral surface, and this effect was more pronounced in the rL537A mutant. We conclude that these wild-type residues in the NDV F CT have an effect on regulating F protein biological functions and thus modulating viral replication and pathogenesis. N ewcastle disease virus (NDV) is a highly prevalent avian pathogen that infects essentially all species of birds and is of major economic importance to the poultry industry (1, 2). The disease varies in degree of severity, ranging from an inapparent infection to outbreaks of severe respiratory and neurologic disease that can have 100% mortality. Based on severity of the disease, NDV strains are grouped into lentogenic (nonpathogenic or mildly pathogenic), mesogenic (moderately pathogenic), and velogenic (highly pathogenic) pathotypes (3). NDV belongs to the genus Avulavirus within the family Paramyxoviridae, a family of enveloped, nonsegmented, negative-sense RNA viruses (4).The envelope of NDV contains two surface glycoproteins, HN and F (5,6). HN mediates viral attachment by binding to sialic acid cellular receptors, and F protein facilitates viral entry into the cells by fusing the viral envelope with the host cell membrane (7,8). The virus fusion process involves a series of major coordinated conformational changes in the F protein that bring together and merges the opposing membranes (5, 9).The NDV F protein ( Fig. 1) is synthesized as an inactive precursor, F 0 (66 kDa), that is cleaved posttranslationally by host cell proteases into two disulfide-linked subunits, N-terminal F 2 (12.5 kDa) and C-terminal F 1 (55 kDa) (8, 10). The F cleavage site is a major determinant of NDV tropism and viru...

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confidence: 94%

Mutations in the Cytoplasmic Domain of the Newcastle Disease Virus Fusion Protein Confer Hyperfusogenic Phenotypes Modulating Viral Replication and Pathogenicity

Samal

Khattar

Paldurai

et al. 2013

J Virol

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“…Moreover, no amino acid substitutions were found at positions 72, 74, 75, 78 and 79 of the F2 protein, which were previously shown to be involved in neutralization [15]. An N-linked glycosylation acceptor site (N-X-S/T, where X corresponds to any amino acid except aspartic acid or proline) at position 85-87 of the F2 protein is also conserved [9,40], as are the cysteine residues at positions 25 and 76 of the F2 protein [41].…”

Section: Resultsmentioning

confidence: 95%

An evolutionary insight into Newcastle disease viruses isolated in Antarctica

et al. 2015

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The disease caused by Newcastle disease virus (NDV) is a severe threat to the poultry industry worldwide. Recently, NDV has been isolated in the Antarctic region. Detailed studies on the mode of evolution of NDV strains isolated worldwide are relevant for our understanding of the evolutionary history of NDV. For this reason, we have performed Bayesian coalescent analysis of NDV strains isolated in Antarctica to study evolutionary rates, population dynamics, and patterns of evolution. Analysis of F protein cleavage-site sequences of NDV isolates from Antarctica suggested that these strains are lentogenic. Strains isolated in Antarctica and genotype I reference strain Ulster/67 diverged from ancestors that existed around 1958. The time of the most recent common ancestor (MRCA) was established to be around 1883 for all class II viruses. A mean rate of evolution of 1.78 × 10(-3) substitutions per site per year (s/s/y) was obtained for the F gene sequences of NDV strains examined in this study. A Bayesian skyline plot indicated a decline in NDV population size in the last 25 years. The results are discussed in terms of the possible role of Antarctica in emerging or re-emerging viruses and the evolution of NDV populations worldwide.

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“…The F proteins of these two strains are highly related, differing by only 8 amino acid assignments. The regions of the F protein in which these amino acid assignment differences occur between strains BC and GBT are the following: the F2 region (P10S and V11A), the F1 ectodomain region (G265S, G304E, and I457T), the transmembrane region (I510T and V520A), and the cytoplasmic tail (T550A) (28). The 3 amino acid assignment differences that occur in the F1 ectodomain region did not fall in the heptad repeat (HR) domains, HR1 and HR2.…”

Section: Discussionmentioning

confidence: 99%

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

Paldurai

Kim

Nayak

et al. 2014

J Virol

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Naturally occurring Newcastle disease virus (NDV) strains vary greatly in virulence. The presence of multibasic residues at the proteolytic cleavage site of the fusion (F) protein has been shown to be a primary determinant differentiating virulent versus avirulent strains. However, there is wide variation in virulence among virulent strains. There also are examples of incongruity between cleavage site sequence and virulence. These observations suggest that additional viral factors contribute to virulence. In this study, we evaluated the contribution of each viral gene to virulence individually and in different combinations by exchanging genes between velogenic (highly virulent) strain GB Texas (GBT) and mesogenic (moderately virulent) strain Beaudette C (BC). These two strains are phylogenetically closely related, and their F proteins contain identical cleavage site sequences, 112 RRQKR2F117 . A total of 20 chimeric viruses were constructed and evaluated in vitro, in 1-day-old chicks, and in 2-week-old chickens. The results showed that both the envelope-associated and polymerase-associated proteins contribute to the difference in virulence between rBC and rGBT, with the envelope-associated proteins playing the greater role. The F protein was the major individual contributor and was sometimes augmented by the homologous M and HN proteins. The dramatic effect of F was independent of its cleavage site sequence since that was identical in the two strains. The polymerase L protein was the next major individual contributor and was sometimes augmented by the homologous N and P proteins. The leader and trailer regions did not appear to contribute to the difference in virulence between BC and GBT. IMPORTANCEThis study is the first comprehensive and systematic study of NDV virulence and pathogenesis. Genetic exchanges between a mesogenic and a velogenic strain revealed that the fusion glycoprotein is the major virulence determinant regardless of the identical virulence protease cleavage site sequence present in both strains. The contribution of the large polymerase protein to NDV virulence is second only to that of the fusion glycoprotein. The identification of virulence determinants is of considerable importance, because of the potential to generate better live attenuated NDV vaccines. It may also be possible to apply these findings to other paramyxoviruses.

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Complete genome sequence of highly virulent neurotropic Newcastle disease virus strain Texas GB

Cited by 20 publications

References 27 publications

Mutations in the Cytoplasmic Domain of the Newcastle Disease Virus Fusion Protein Confer Hyperfusogenic Phenotypes Modulating Viral Replication and Pathogenicity

Mutations in the Cytoplasmic Domain of the Newcastle Disease Virus Fusion Protein Confer Hyperfusogenic Phenotypes Modulating Viral Replication and Pathogenicity

An evolutionary insight into Newcastle disease viruses isolated in Antarctica

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

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