Comparative biology of two genetically closely related Newcastle disease virus strains with strongly contrasting pathogenicity

Chen, Xi; Chen, Siqi; Chen, Haotian; Tian, Jianxia; Zhao, Xueliang; Jia, Yanqing; Xiao, Sa; Wang, Xinglong; Liu, Haijin; Yang, Zhicong

doi:10.1016/j.vetmic.2020.108977

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…Genotype VII NDV strains predominate in China, with sub-genotype VII strains isolated from different provinces and cities throughout China, particularly in the south and southeast ( Xiang et al, 2020 ; Chen et al, 2021 ). Currently, the primary methods for sequencing viral genomes are Sanger and high-throughput sequencing.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Chicken-Derived Genotype VII Newcastle Disease Virus Isolates from Northwest China

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Characterization of Chicken-Derived Genotype VII Newcastle Disease Virus Isolates from Northwest China

et al. 2023

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“…Multiple studies have shown that mutations in the HN protein are considered as determinants of in vivo biological activities, such as virulence and pathogenicity [43,44]. We have previously demonstrated that the aa mutations in the HN protein were required for the virulence and pathogenicity of genotype III NDV, but the research content needs to be further enriched.…”

Section: Discussionmentioning

confidence: 99%

Biological Significance of Dual Mutations A494D and E495K of the Genotype III Newcastle Disease Virus Hemagglutinin-Neuraminidase In Vitro and In Vivo

Lü

Zhan

Liu

et al. 2022

Viruses

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As a multifunctional protein, the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is involved in various biological functions. A velogenic genotype III NDV JS/7/05/Ch evolving from the mesogenic vaccine strain Mukteswar showed major amino acid (aa) mutations in the HN protein. However, the precise biological significance of the mutant HN protein remains unclear. This study sought to investigate the effects of the mutant HN protein on biological activities in vitro and in vivo. The mutant HN protein (JS/7/05/Ch-type HN) significantly enhanced the hemadsorption (HAd) and fusion promotion activities but impaired the neuraminidase (NA) activity compared with the original HN protein (Mukteswar-type HN). Notably, A494D and E495K in HN exhibited a synergistic role in regulating biological activities. Moreover, the mutant HN protein, especially A494D and E495K in HN, enhanced the F protein cleavage level, which can contribute to the activation of the F protein. In vitro infection assays further showed that NDVs bearing A494D and E495K in HN markedly impaired the cell viability. Simultaneously, A494D and E495K in HN enhanced virus replication levels at the early stage of infection but weakened later in infection, which might be associated with the attenuated NA activity and cell viability. Furthermore, the animal experiments showed that A494D and E495K in HN enhanced case fatality rates, virus shedding, virus circulation, and histopathological damages in NDV-infected chickens. Overall, these findings highlight the importance of crucial aa mutations in HN in regulating biological activities of NDV and expand the understanding of the enhanced pathogenicity of the genotype III NDV.

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“…After 3 days of incubation, the cells were harvested and inoculated into 9-day-old SPF chicken embryos to rescue the viruses. After 3 days, the allantoic fluid was harvested and checked by using a haemagglutination (HA) assay [ 17 ]. Viral RNA was extracted from HA-positive allantoic fluid according to the manufacturer’s protocol supplied with a StarSpin Animal RNA Mini Kit (Genstar, Beijing, China), and cDNA was synthesized from viral RNA using a reverse transcription PCR kit (Genstar, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have reported the derivation of a lentogenic NDV virus from a mesogenic strain through sequential passages in chick embryos. Sequence analysis has revealed that the two homologous strains share the same F protein but differ in HN, with two aa substitutions [ 17 ]. Therefore, we hypothesized that these two aa sites may lead to changes in the functions of the HN protein that ultimately cause the difference in virulence between the two strains.…”

Section: Introductionmentioning

confidence: 99%

Identification of a new amino acid mutation in the HN protein of NDV involved in pathogenicity

Chen

Jia

Wei

et al. 2021

Vet Res

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The fusion (F) and haemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are viral entry proteins and are recognized as the major virulence determinants. Previously, a lentogenic NDV virus (CE16) was derived from a mesogenic strain (CI10) through sequential passages in chick embryos. Whole-genome sequence analysis revealed that the two homologous strains shared the same F protein but differed in HN with two amino acid (aa) substitutions (A215G and T430A). To elucidate the molecular reasons for virulence attenuation, two original plasmids (HN-CI10 and HN-CE16) and two single-point mutants (G215A and A430T) reverse-mutated from HN-CE16 were constructed to analyse the known biological functions of HN. The results showed that the A430T substitution significantly weakened the haemadsorption (HAd) activity, increased the neuraminidase (NA) activity, improved the fusion-promoting activity, and enhanced the cleavage-promoting activity of HN-CE16. However, G215A failed to induce obvious functional changes. Therefore, the aa residue HN430 may play a key role in determining virulence. To test this hypothesis, further studies on A430T were conducted through reverse genetics using an infectious cDNA clone. At the viral level, the A430T-mutated virus showed dramatic promotion of viral plaque formation, propagation, and pathogenicity in vitro and in vivo. This study demonstrates a new virulence site associated with HN protein functions, viral propagation, and pathogenicity. All these findings could lay a foundation for illuminating the molecular mechanism of NDV virulence.

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Comparative biology of two genetically closely related Newcastle disease virus strains with strongly contrasting pathogenicity

Cited by 9 publications

References 20 publications

Characterization of Chicken-Derived Genotype VII Newcastle Disease Virus Isolates from Northwest China

Characterization of Chicken-Derived Genotype VII Newcastle Disease Virus Isolates from Northwest China

Biological Significance of Dual Mutations A494D and E495K of the Genotype III Newcastle Disease Virus Hemagglutinin-Neuraminidase In Vitro and In Vivo

Identification of a new amino acid mutation in the HN protein of NDV involved in pathogenicity

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