High levels of virus replication and an intense inflammatory response contribute to the severe pathology in lymphoid tissues caused by Newcastle disease virus genotype VIId

Hu, Zenglei; Hu, Jiao; Hu, Shunlin; Song, Qing; Ding, Pingyun; Jun, Zhu; Liu, Xiaowen; Wang, Xiaoquan

doi:10.1007/s00705-014-2301-2

Cited by 52 publications

(62 citation statements)

References 22 publications

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“…NDV infection induced strong pro-inflammatory responses that played an important role in viral pathogenesis. The IL-2/6/1β and IFN-β mRNA expression levels were increased in the oviductal tissues of NDV-infected hens; our data are consistent with previous findings [9–12]. The expression of the IL-2 gene in the peripheral blood of F48E9 NDV-infected chickens in a previous study fluctuated and did not exhibit a significant difference compared with the control group during the experimental period [26].…”

Section: Discussionsupporting

confidence: 92%

“…IFN-α belongs to the type I interferon family and can be produced in most cells after virus infection, whereupon it localizes to the site of viral infection and inhibits viral replication. In this study, IFN-α experienced a decline in the magnum of hen oviducts 3 dpi; the same phenomenon was reported in another study that demonstrated that the expression of IFN-α experienced a sharp decline in the peripheral blood of F48E9 NDV-infected chicken 7 dpi [12], which might contribute to rapid viral replication. The highest levels of expression of the examined genes corresponded with the significant clinical signs and the inflammatory responses in the oviductal tissues.…”

Section: Discussionsupporting

confidence: 84%

“…These involve intense inflammatory responses in the form of a cytokine storm that are initiated inside infected cells or tissues following viral replication and result in excessive cellular apoptosis and tissue damage. In vivo studies suggested that NDV initiated strong immune responses in the spleen, lymph nodes and peripheral blood of infected chickens, where the mRNA expression levels of proinflammatory and cytokines/chemokines were significantly upregulated [9–12]. Strong innate immune response and cell death were observed in chicken splenocytes infected with genotype VIId NDV [13].…”

Section: Introductionmentioning

confidence: 99%

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Strong inflammatory responses and apoptosis in the oviducts of egg-laying hens caused by genotype VIId Newcastle disease virus

Guo

Liu

et al. 2016

BMC Vet Res

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BackgroundNewcastle disease virus (NDV) can cause serious damage to the reproductive tracts of egg-laying hens and leads to egg production and quality reduction. However, the mechanism of severe pathological damage in the oviducts of egg-laying hens after NDV infection has not been fully elucidated. In this study, the correlation between the primary pathological lesions and viral load in the oviducts of egg-laying hens infected with the velogenic genotype VIId NDV strain was evaluated by pathological observation and virus detection. Subsequently, apoptosis, the expression of immune-related genes and lymphocyte infiltration into the infected oviducts were determined to explore the potential causes of the pathological changes.ResultsA higher viral load and severe tissue lesions and apoptotic bodies were observed in the oviduct of NDV-infected hens compared with the control. Immune-related genes, including TLR3/7/21, MDA5, IL-2/6/1β, IFN-β, CXCLi1/2, and CCR5, were significantly upregulated in the magnum and uterus. IL-2 presented the highest mRNA level change (137-fold) at 5 days post infection (dpi) in the magnum. Infection led to CD3+CD4+ and CD3+CD8α+ lymphocyte infiltration into the magnum of the oviduct. A higher viral load was found to be associated with pathological changes and the elevated expression of proinflammatory cytokines in the NDV-infected hens.ConclusionsOur results indicate that the severe lesions and apoptosis in the oviducts of egg-laying hens caused by genotype VIId NDV strains are associated with the excessive release of inflammatory cytokines, chemokines and lymphocyte infiltration, which contribute to the dysfunction of the oviducts and the decrease of egg production in hens.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Strong inflammatory responses and apoptosis in the oviducts of egg-laying hens caused by genotype VIId Newcastle disease virus

Guo

Liu

et al. 2016

BMC Vet Res

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“…Genotype VII viruses within class II that merged decades ago are now the major genotype of virus that are circulating in different countries including China [3]. The genome of NDV is approximately 15kb and encodes 6 structural proteins including nucleoprotein (NP), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin-neuraminidase (HN), the large protein (L), and two nonstructual proteins V and W. The NDV strains can be grouped as highly (velogenic), moderately (mesogenic), and weakly pathogenic (lentogenic) pathotypes according to cleavage site of fusion (F) gene which works as a virulence-determine gene [4].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a Recombinant Genotype VII Vaccine against Challenge with Velogenic Newcastle Disease Virus

Cheng¹,

Sheng²,

Li³

et al. 2016

J Vaccines Immunol

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Background: Newcastle disease virus (NDV) genotype VII has become the dominant genotype in China. However, NDV genotype II was used to make current commercial NDV vaccines. The mismatch of genotypes between circulating and vaccine strains of viruses may compromise the efficacy of vaccines. Methods:In this study, a current circulating NDV was attenuated by mutations of multiple basic amino acid motif of fusion cleavage site 112 RRQKGF 117 based on reverse genetic techniques. The recombinant virus was prepared as an inactivated vaccine to test its efficacy and compared with a commercial LaSota NDV vaccine on SPF chickens.Results: All vaccinated chickens survived by the end of the study. By contrast, the unvaccinated chickens were all dead before 5 days post-challenge (DPC). Compared to commercial LaSota vaccine, the experimental inactivated vaccine elicited earlier and higher titer of HI antibodies and had reduced titer and duration of virus shedding after challenge. Conclusion:The experimental inactivated NDV vaccine may work as a promising vaccine candidate to control the disease.NDV genotype II strains [7]. The cross-protection of vaccines to genotype VII virus was seldom explored. In this study, we developed an inactivated NDV genotype VII vaccine based on reverse genetic techniques and compared its efficacy with commercial LaSota vaccine on SPF chickens. Material and methods VirusNDV strain PLK-N-06 was isolated from an outbreak of ND in chickens and identified as velogenic [intracerebral pathogenicity index (ICPI) = 1.79, mean death time (MDT) = 49 h]. Phylogenetic analysis results showed that it belongs to NDV genotype VIId. The virus was grown in 10-day-old embryonated SPF chicken eggs. Allantoic fluid was collected for use.

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“…21 Increased virus replication and a greater inflammatory response within lymphoid tissues has been associated with increased pathogenicity of velogenic ND viruses. 164 The results of our study indicate that the low pathogenicity of the Meredith/02 virus must be attributed to regions of the viral genome other than the F protein cleavage site, given that the cleavage site contains a virulent motif. 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.…”

Section: Discussionmentioning

confidence: 70%

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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High levels of virus replication and an intense inflammatory response contribute to the severe pathology in lymphoid tissues caused by Newcastle disease virus genotype VIId

Cited by 52 publications

References 22 publications

Strong inflammatory responses and apoptosis in the oviducts of egg-laying hens caused by genotype VIId Newcastle disease virus

Strong inflammatory responses and apoptosis in the oviducts of egg-laying hens caused by genotype VIId Newcastle disease virus

Efficacy of a Recombinant Genotype VII Vaccine against Challenge with Velogenic Newcastle Disease Virus

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

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