Publications by authors named "Christian Grund"

74 Publications

Antigenic and Molecular Characterization of Virulent Newcastle Disease Viruses Circulating in Ethiopia Between 1976 and 2008.

Vet Med (Auckl) 2021 4;12:129-140. Epub 2021 Jun 4.

Institute of Infectology, Friedrich-Loeffler-Institut, Greifswald, Germany.

Introduction: Newcastle disease virus (NDV) cultures held in the isolate collections in Ethiopia between 1976 and 2008 were not characterized using biological and molecular techniques. The already characterized NDV isolates belonged to genotype VI but the genetic nature of previously collected isolates, which could shade light on the history of introduction into the country and their evolutionary relationships, were not established.

Methods: A total of 14 NDVs (11 obtained from outbreak cases in chickens and three commercial vaccinal strains used in the country) were inoculated into specific pathogen free (SPF) embryonated chicken eggs (ECE). Allantoic fluids harvested from grown SPF ECE were tested by heamagglutination (HA) and heamagglutination inhibition (HI) tests. Partial F gene sequences were generated for all samples and molecular evolutionary relationships were reconstructed together with reference sequences freely available online. The pathogenicities of the isolates were assessed in vivo by determining their intracerebral pathogenicity index (ICPI) in day-old chicks and molecularly by determination of F gene cleavage sites.

Results: Of these, 12 viruses (two vaccines and 10 outbreaks) were successfully propagated as evidenced by a positive heamagglutination (HA) test. These 12 propagated viruses were further characterized by heamagglutination inhibition (HI) test, of which only three viruses reacted with monoclonal antibody (MAb 617/616) specific for pigeon paramyxovirus-1. In addition, all 14 viruses were characterized by partial fusion (F) gene sequencing and phylogenetic tree reconstruction. The Ethiopian NDV isolates clustered with genotype VI viruses, forming two clades (groups 1 and 2) that have ancestral relationships with Egypt-1990 and Sudan-1975 like viruses.

Discussion: The characterized genotype VI NDVs were genetically similar to currently circulating NDVs in Ethiopia. The isolates had cleavage sites consistent with mesogenic/velogenic NDV with a mean ICPI value of 1.76, indicating that the isolates were velogenic. Two and four highly virulent viruses were thermostable at 56°C for 2 hours and 1 hour, respectively. To reduce chicken mortality and production losses, proper control of the disease should be instituted using high quality and protective vaccines together with strong biosecurity measures.
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http://dx.doi.org/10.2147/VMRR.S297281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187085PMC
June 2021

A Semiquantitative Scoring System for Histopathological and Immunohistochemical Assessment of Lesions and Tissue Tropism in Avian Influenza.

Viruses 2021 05 9;13(5). Epub 2021 May 9.

Institute of Veterinary Pathology, Leipzig University, 04103 Leipzig, Germany.

The main findings of the post-mortem examination of poultry infected with highly pathogenic avian influenza viruses (HPAIV) include necrotizing inflammation and viral antigen in multiple organs. The lesion profile displays marked variability, depending on viral subtype, strain, and host species. Therefore, in this study, a semiquantitative scoring system was developed to compare histopathological findings across a wide range of study conditions. Briefly, the severity of necrotizing lesions in brain, heart, lung, liver, kidney, pancreas, and/or lymphocytic depletion in the spleen is scored on an ordinal four-step scale (0 = unchanged, 1 = mild, 2 = moderate, 3 = severe), and the distribution of the viral antigen in parenchymal and endothelial cells is evaluated on a four-step scale (0 = none, 1 = focal, 2 = multifocal, 3 = diffuse). These scores are used for a meta-analysis of experimental infections with H7N7 and H5N8 (clade 2.3.4.4b) HPAIV in chickens, turkeys, and ducks. The meta-analysis highlights the rather unique endotheliotropism of these HPAIV in chickens and a more severe necrotizing encephalitis in H7N7-HPAIV-infected turkeys. In conclusion, the proposed scoring system can be used to condensate HPAIV-typical pathohistological findings into semiquantitative data, thus enabling systematic phenotyping of virus strains and their tissue tropism.
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http://dx.doi.org/10.3390/v13050868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151536PMC
May 2021

Comparison of genomic and antigenic properties of Newcastle Disease virus genotypes II, XXI and VII from Egypt do not point to antigenic drift as selection marker.

Transbound Emerg Dis 2021 May 6. Epub 2021 May 6.

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Diagnostic Virology, Greifswald Insel-Riems, Germany.

Newcastle disease (ND), caused by avian orthoavulavirus type-1 (NDV), is endemic in poultry in many regions of the world and causes continuing outbreaks in poultry populations. In the Middle East, genotype XXI, used to be present in poultry in Egypt but has been replaced by genotype VII. We investigated whether virus evolution contributed to superseding and focussed on the antigenic sites within the hemagglutinin-neuraminidase (HN) spike protein. Full-length sequences of an NDV genotype VII isolate currently circulating in Egypt was compared to a genotype XXI isolate that was present as co-infection with vaccine-type viruses (II) in a historical virus isolated in 2011. Amino acid differences in the HN glycoprotein for both XXI and VII viruses amounted to 11.7% and 11.9%, respectively, compared to the La Sota vaccine type. However, mutations within the globular head (aa 126-570), bearing relevant antigenic sites, were underrepresented (a divergence of 8.8% and 8.1% compared to 22.4% and 25.6% within the protein domains encompassing cytoplasmic tail, transmembrane part and stalk regions (aa 1-125) for genotypes XXI and VII, respectively). Nevertheless, reaction patterns of HN-specific monoclonal antibodies inhibiting receptor binding revealed differences between vaccine-type viruses and genotype XXI and VII viruses for epitopes located in the head domain. Accordingly, compared to Egyptian vaccine-type isolates and the La Sota vaccine reference strain, single aa substitutions in 6 of 10 described neutralizing epitopes of HN were found. However, the same alterations in neutralization sensitive epitopes were present in old genotype XXI as well as in newly emerged genotype VII isolates. In addition, isolates were indistinguishable by polyclonal chicken sera raised against different genotypes including vaccine viruses. These findings suggest that factors other than antigenic differences within the HN protein account for facilitating the spread of genotype VII versus genotype XXI viruses in Egypt.
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http://dx.doi.org/10.1111/tbed.14121DOI Listing
May 2021

Vaccine Quality Is a Key Factor to Determine Thermal Stability of Commercial Newcastle Disease (ND)Vaccines.

Vaccines (Basel) 2021 Apr 9;9(4). Epub 2021 Apr 9.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Edinburgh EH26 0PZ, UK.

Vaccination against Newcastle disease (ND), a devastating viral disease of chickens, is often hampered by thermal inactivation of the live vaccines, in particular in tropical and hot climate conditions. In the past, "thermostable" vaccine strains (I-2) were proposed to overcome this problem but previous comparative studies did not include formulation-specific factors of commercial vaccines. In the current study, we aimed to verify the superior thermal stability of commercially formulated I-2 strains by comparing six commercially available ND vaccines. Subjected to 37 °C as lyophilized preparations, two vaccines containing I-2 strains were more sensitive to inactivation than a third I-2 vaccine or compared to three other vaccines based on different ND strains. However, reconstitution strains proved to have a comparable tenacity. Interestingly, all vaccines still retained a sufficient virus dose for protection (10 EID) after 1 day at 37 °C. These results suggest that there are specific factors that influence thermal stability beyond the strain-specific characteristics. Exposing ND vaccines to elevated temperatures of 51 and 61 °C demonstrated that inactivation of all dissolved vaccines including I-2 vaccine strains occurred within 2 to 4 h. The results revealed important differences among the vaccines and emphasize the importance of the quality of a certain vaccine preparation rather than the strain it contains. These data highlight that regardless of the ND strain used for vaccine preparation, the appropriate cold chain is mandatory for keeping live ND vaccines efficiency in hot climates.
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http://dx.doi.org/10.3390/vaccines9040363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069011PMC
April 2021

The Role of Employees' Age for the Relation Between Job Autonomy and Sickness Absence.

J Occup Environ Med 2021 Apr 28. Epub 2021 Apr 28.

RWTH Aachen University, School of Business and Economics, Human Resource Management and Personnel Economics, Aachen, Germany (Dr Grund and Rubin).

Objective: We investigate whether job autonomy is associated with employees' sickness absence. In particular, we examine the role of employees' age for this relationship.

Methods: We can make use of the representative German Study of Mental Health at Work data (n = 3099 employees) and control for relevant covariates.

Results: Applying theoretical consideration such as the Job Demand Control Model, we do find evidence for an inverse relation between employees' job autonomy and days of sickness absence. This relation is only weakly mediated by job satisfaction and particularly relevant for more senior employees.

Conclusions: Theoretical implications are aimed at extending the existing theoretical models by individuals age and derive age-specific propositions. Managerial implications include recommendations which directly affect the individuals work content with regard to the use of our definition of job autonomy.
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http://dx.doi.org/10.1097/JOM.0000000000002239DOI Listing
April 2021

Monoclonal antibodies specific for the hemagglutinin-neuraminidase protein define neutralizing epitopes specific for Newcastle disease virus genotype 2.VII from Egypt.

Virol J 2021 Apr 26;18(1):86. Epub 2021 Apr 26.

Institute for Diagnostic Virology, Friedrich-Loeffler-Institute, Südufer 10, 17493, Greifswald-Insel Riems, Germany.

Background: Newcastle disease is a devastating disease in poultry caused by virulent Newcastle disease virus (NDV), a paramyxovirus endemic in many regions of the world despite intensive vaccination. Phylogenetic analyses reveal ongoing evolution of the predominant circulating genotype 2.VII, and the relevance of potential antigenic drift is under discussion. To investigate variation within neutralization-sensitive epitopes within the protein responsible for receptor binding, i.e. the Hemagglutinin-Neuraminidase (HN) spike protein, we were interested in establishing genotype-specific monoclonal antibodies (MAbs).

Methods: An HN-enriched fraction of a gradient-purified NDV genotype 2.VII was prepared and successfully employed to induce antibodies in BalbC mice that recognize conformationally intact sites reactive by haemagglutination inhibition (HI). For subsequent screening of mouse hybridoma cultures, an NDV-ELISA was established that utilizes Concanavalin A (ConA-ELISA) coupled glycoproteins proven to present conformation-dependent epitopes.

Results: Six out of nine selected MAbs were able to block receptor binding as demonstrated by HI activity. One MAb recognized an epitope only present in the homologue virus, while four other MAbs showed weak reactivity to selected other genotypes. On the other hand, one broadly cross-reacting MAb reacted with all genotypes tested and resembled the reactivity profile of genotype-specific polyclonal antibody preparations that point to minor antigenic differences between tested NDV genotpyes.

Conclusions: These results point to the concurrent presence of variable and conserved epitopes within the HN molecule of NDV. The described protocol should help to generate MAbs against a variety of NDV strains and to enable in depth analysis of the antigenic profiles of different genotypes.
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http://dx.doi.org/10.1186/s12985-021-01540-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072307PMC
April 2021

Neuraminidase-associated plasminogen recruitment enables systemic spread of natural avian Influenza viruses H3N1.

PLoS Pathog 2021 Apr 23;17(4):e1009490. Epub 2021 Apr 23.

Institute of Diagnostic Virology, Greifswald-Insel Riems, Germany.

Repeated outbreaks due to H3N1 low pathogenicity avian influenza viruses (LPAIV) in Belgium were associated with unusually high mortality in chicken in 2019. Those events caused considerable economic losses and prompted restriction measures normally implemented for eradicating high pathogenicity avian influenza viruses (HPAIV). Initial pathology investigations and infection studies suggested this virus to be able to replicate systemically, being very atypical for H3 LPAIV. Here, we investigate the pathogenesis of this H3N1 virus and propose a mechanism explaining its unusual systemic replication capability. By intravenous and intracerebral inoculation in chicken, we demonstrate systemic spread of this virus, extending to the central nervous system. Endoproteolytic viral hemagglutinin (HA) protein activation by either tissue-restricted serine peptidases or ubiquitous subtilisin-like proteases is the functional hallmark distinguishing (H5 or H7) LPAIV from HPAIV. However, luciferase reporter assays show that HA cleavage in case of the H3N1 strain in contrast to the HPAIV is not processed by intracellular proteases. Yet the H3N1 virus replicates efficiently in cell culture without trypsin, unlike LPAIVs. Moreover, this trypsin-independent virus replication is inhibited by 6-aminohexanoic acid, a plasmin inhibitor. Correspondingly, in silico analysis indicates that plasminogen is recruitable by the viral neuraminidase for proteolytic activation due to the loss of a strongly conserved N-glycosylation site at position 130. This mutation was shown responsible for plasminogen recruitment and neurovirulence of the mouse brain-passaged laboratory strain A/WSN/33 (H1N1). In conclusion, our findings provide good evidence in natural chicken strains for N1 neuraminidase-operated recruitment of plasminogen, enabling systemic replication leading to an unusual high pathogenicity phenotype. Such a gain of function in naturally occurring AIVs representing an established human influenza HA-subtype raises concerns over potential zoonotic threats.
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http://dx.doi.org/10.1371/journal.ppat.1009490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118554PMC
April 2021

Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020.

Emerg Microbes Infect 2021 Dec;10(1):148-151

Department of Virology, Animal and Plant Health Agency, OIE/FAO International Reference Laboratory for Avian Influenza, Swine Influenza and Newcastle Disease Virus, Surrey, UK.

Analyses of HPAI H5 viruses from poultry outbreaks across a wide Eurasian region since July 2020 including the Russian Federation, Republics of Iraq and Kazakhstan, and recent detections in migratory waterfowl in the Netherlands, revealed undetected maintenance of H5N8, likely in galliform poultry since 2017/18 and both H5N5 and H5N1. All viruses belong to A/H5 clade 2.3.4.4b with closely related HA genes. Heterogeneity in Eurasian H5Nx HPAI emerging variants threatens poultry production, food security and veterinary public health.
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http://dx.doi.org/10.1080/22221751.2021.1872355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832535PMC
December 2021

Protection of Chickens with Maternal Immunity Against Avian Influenza Virus (AIV) by Vaccination with a Novel Recombinant Newcastle Disease Virus Vector.

Avian Dis 2020 12;64(4):427-436

Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

Newcastle disease virus (NDV) vectors expressing avian influenza virus (AIV) hemagglutinin of subtype H5 protect specific pathogen-free chickens from Newcastle disease and avian influenza. However, maternal AIV antibodies (AIV-MDA+) are known to interfere with active immunization by influencing vaccine virus replication and gene expression, resulting in inefficient protection. To overcome this disadvantage, we inserted a transgene encoding a truncated soluble hemagglutinin (HA) in addition to the gene encoding membrane-bound HA from highly pathogenic avian influenza virus (HPAIV) H5N1 into lentogenic NDV Clone 30 genome (rNDVsolH5_H5) to overexpress H5 antigen. Vaccination of 3-wk-old AIV-MDA+ chickens with rNDVsolH5_H5 and subsequent challenge infection with HPAIV H5N1 3 wk later resulted in 100% protection. Vaccination of younger chickens with higher AIV-MDA levels 1 and 2 wk after hatch resulted in protection rates of 40% and 85%, respectively. However, all vaccinated chickens showed strongly reduced shedding of challenge virus compared with age-matched, nonvaccinated control chickens. All control chickens succumbed to the HPAIV infection with a grading in disease progression between the three groups, indicating the influence of AIV-MDAs even at a low level. Furthermore, the shedding and serologic data gathered after immunization indicate sufficient replication of the vaccine virus, which leads to the assumption that lower protection rates in younger AIV-MDA+ chickens are caused by an H5 antigen-specific block and not by the interference of the AIV-MDA and the vaccine virus itself. In summary, solid protective efficacy and reduced virus transmission were achieved in 3-wk-old AIV-MDA+ chickens, which is relevant especially in regions endemically infected with HPAIV H5N1.
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http://dx.doi.org/10.1637/aviandiseases-D-20-00014DOI Listing
December 2020

SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study.

Lancet Microbe 2020 Sep 7;1(5):e218-e225. Epub 2020 Jul 7.

Institute of Diagnostic Virology, Greifswald-Insel Riems, Germany.

Background: In December, 2019, a novel zoonotic severe acute respiratory syndrome-related coronavirus emerged in China. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became pandemic within weeks and the number of human infections and severe cases is increasing. We aimed to investigate the susceptibilty of potential animal hosts and the risk of anthropozoonotic spill-over infections.

Methods: We intranasally inoculated nine fruit bats (), ferrets (), pigs (), and 17 chickens () with 10 TCID of a SARS-CoV-2 isolate per animal. Direct contact animals (n=3) were included 24 h after inoculation to test viral transmission. Animals were monitored for clinical signs and for virus shedding by nucleic acid extraction from nasal washes and rectal swabs (ferrets), oral swabs and pooled faeces samples (fruit bats), nasal and rectal swabs (pigs), or oropharyngeal and cloacal swabs (chickens) on days 2, 4, 8, 12, 16, and 21 after infection by quantitative RT-PCR (RT-qPCR). On days 4, 8, and 12, two inoculated animals (or three in the case of chickens) of each species were euthanised, and all remaining animals, including the contacts, were euthanised at day 21. All animals were subjected to autopsy and various tissues were collected for virus detection by RT-qPCR, histopathology immunohistochemistry, and in situ hybridisation. Presence of SARS-CoV-2 reactive antibodies was tested by indirect immunofluorescence assay and virus neutralisation test in samples collected before inoculation and at autopsy.

Findings: Pigs and chickens were not susceptible to SARS-CoV-2. All swabs, organ samples, and contact animals were negative for viral RNA, and none of the pigs or chickens seroconverted. Seven (78%) of nine fruit bats had a transient infection, with virus detectable by RT-qPCR, immunohistochemistry, and in situ hybridisation in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung, and lung-associated lymphatic tissue in two animals euthanised at day 4. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets, with transmission to all three direct contact animals. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Prominent viral RNA loads of 0-10 viral genome copies per mL were detected in the upper respiratory tract of fruit bats and ferrets, and both species developed SARS-CoV-2-reactive antibodies reaching neutralising titres of up to 1/1024 after 21 days.

Interpretation: Pigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. Ferrets might serve as a useful model for further studies-eg, testing vaccines or antivirals.

Funding: German Federal Ministry of Food and Agriculture.
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http://dx.doi.org/10.1016/S2666-5247(20)30089-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340389PMC
September 2020

Emerging infectious bronchitis virus (IBV) in Egypt: Evidence for an evolutionary advantage of a new S1 variant with a unique gene 3ab constellation.

Infect Genet Evol 2020 Nov 1;85:104433. Epub 2020 Jul 1.

Institute of Diagnostic Virology Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Germany. Electronic address:

Infectious bronchitis virus (IBV), a gamma-coronavirus, causes infectious bronchitis (IB), a major respiratory disease of chicken. Its high mutation rate in conjunction with recombination of the RNA genome constantly creates IBV variants that are difficult to control by currently available vaccines. In this study, we addressed the question whether small-scale holdings might harbor IBV variants that serve as a reservoir for newly emerging variants. Egyptian IBV isolate EGY/NR725/2016 (NR725/16) from a small-scale broiler farm was assigned to genotype I, clade 23 (S1:GI-23), based on partial S1 gene sequences and corroborated by full genome sequencing. Analysis of the S1 gene established three subclades for historical IBV strains (S1:GI-23.1, S1:GI-23.2.1 and S1:GI-23.2.2) and confirmed NR725/16 as being part of a separate fourth subclade (S1:GI-23.3). Samples from the years 2018 and 2019 revealed that the new subclade prevails in Egypt, carrying fixed mutations within the hypervariable regions (HVR) 1-3 of the S1 protein that affect two neutralization sensitive epitopes at sites 294F, 297S and 306Y (48.2) and 329R (62.1). In addition, recombination was recognized in isolate NR 725/16, with intra-subtype mixing for the entire genes 3ab and E and inter-subtype mixing for the entire gene 6b with a close match to QX like viruses of genotype GI-19. Further analysis of gene 3ab detected the homologous gene pool to NR725/16 in samples from 2013 (3ab:C) and closely related 3ab genotypes in IBV Egyptian isolates from 2016, 2018 and 2019. These data prove a flourishing exchange between poultry holdings with a common gene pool. The continued circulation of viruses harboring genes S1:GI-23.3 and 3ab:C indicates an evolutionary advantage of this combination possibly by combining antigenic escape with modulated pathogenicity to facilitate IBV spread in the vaccinated poultry population in Egypt.
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http://dx.doi.org/10.1016/j.meegid.2020.104433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327463PMC
November 2020

A Novel Recombinant Newcastle Disease Virus Vectored DIVA Vaccine against Peste des Petits Ruminants in Goats.

Vaccines (Basel) 2020 Apr 28;8(2). Epub 2020 Apr 28.

Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

Peste des petits ruminants virus (PPRV, species: ) is the causative agent of the eponymous notifiable disease, the peste des petits ruminants (PPR) in wild and domestic sheep and goats. Mortality rates vary between 50% and 100%, causing significant losses of estimated 1.5 to 2 billion US Dollars per year. Live-attenuated PPRV vaccine strains are used in the field for disease prevention, but the application of a more thermostable vaccine enabling differentiation between infected and vaccinated animals (DIVA) would be highly desirable to achieve the goal of global disease eradication. We generated a recombinant Newcastle disease virus (rNDV) based on the live-attenuated NDV Clone 30 that expresses the surface protein hemagglutinin (H) of PPRV strain Kurdistan/11 (rNDV_H). In vitro analyses confirmed transgene expression as well as virus replication in avian, caprine, and ovine cells. Two consecutive subcutaneous vaccinations of German domestic goats with rNDV_H prevented clinical signs and hematogenic dissemination after an intranasal challenge with virulent PPRV Kurdistan/11. Virus shedding by different routes was reduced to a similar extent as after vaccination with the live-attenuated PPRV strain Nigeria 75/1. Goats that were either not vaccinated or inoculated with parental rNDV were used as controls. In summary, we demonstrate in a proof-of-concept study that an NDV vectored vaccine can protect against PPR. Furthermore, it provides DIVA-applicability and a high thermal tolerance.
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http://dx.doi.org/10.3390/vaccines8020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348985PMC
April 2020

Comparison of pathogenicity of subtype H9 avian influenza wild-type viruses from a wide geographic origin expressing mono-, di-, or tri-basic hemagglutinin cleavage sites.

Vet Res 2020 Mar 31;51(1):48. Epub 2020 Mar 31.

Institute of Diagnostic Virology, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute (FLI), Suedufer 10, 17493, Greifswald-Insel Riems, Germany.

An intravenous pathogenicity index (IVPI) of > 1.2 in chickens or, in case of subtypes H5 and H7, expression of a polybasic hemagglutinin cleavage site (HACS), signals high pathogenicity (HP). Viruses of the H9N2-G1 lineage, which spread across Asia and Africa, are classified to be of low pathogenicity although, in the field, they became associated with severe clinical signs and epizootics in chickens. Here we report on a pre-eminent trait of recent H9N2-G1 isolates from Bangladesh and India, which express a tribasic HACS (motif PAKSKR-GLF; reminiscent of an HPAIV-like polybasic HACS) and compare their features to H9Nx viruses with di- and monobasic HACS from other phylogenetic and geographic origins. In an in vitro assay, the tribasic HACS of H9N2 was processed by furin-like proteases similar to bona fide H5 HPAIV while some dibasic sites showed increased cleavability but monobasic HACS none. Yet, all viruses remained trypsin-dependent in cell culture. In ovo, only tribasic H9N2 viruses were found to replicate in a grossly extended spectrum of embryonic organs. In contrast to all subtype H5/H7 HPAI viruses, tribasic H9N2 viruses did not replicate in endothelial cells either in the chorio-allantoic membrane or in other embryonic tissues. By IVPI, all H9Nx isolates proved to be of low pathogenicity. Pathogenicity assessment of tribasic H9N2-G1 viruses remains problematic. It cannot be excluded that the formation of a third basic amino acid in the HACS forms an intermediate step towards a gain in pathogenicity. Continued observation of the evolution of these viruses in the field is recommended.
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http://dx.doi.org/10.1186/s13567-020-00771-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106749PMC
March 2020

Modulation of lethal HPAIV H5N8 clade 2.3.4.4B infection in AIV pre-exposed mallards.

Emerg Microbes Infect 2020 23;9(1):180-193. Epub 2020 Jan 23.

Friedrich-Loeffler-Institut, Greifswald, Germany.

In 2016/2017, a severe epidemic of HPAIV H5N8 clade 2.3.4.4 group B (H5N8B) affected Europe. To analyse the role of mallards in the spatiotemporal dynamics of global HPAIV H5N8B dispersal, mallards (), naturally exposed to various AIV and therefore seropositive, were challenged with H5N8B. All experiments were controlled by infection and co-housing of seronegative juvenile Pekin ducklings. All ducks that survived the first infection were re-challenged 21 dpi with the homologous H5N8B strain. After the first H5N8B infection, seropositive mallards showed only mild clinical symptoms. Moderate to low viral shedding, occurring particularly from the oropharynx and lasting for 7 days maximum, led to severe clinical disease of all contact ducklings. All challenged seronegative Pekin ducks and contact ducklings died or had to be euthanized. H5-specific antibodies were detected in surviving birds within 2 weeks. Virus and viral RNA could be isolated from several water samples until 6 and 9 dpi, respectively. Conversely, upon re-infection with homologous H5N8B neither inoculated nor contact ducklings showed any clinical symptoms, nor was an antibody titer increase of seropositive mallards or any seroconversion of contact ducklings observed. Mallard ducks naturally pre-exposed to LPAIV can play a role as a clinically unsuspicious virus reservoir for H5N8B effective in virus transmission. Mallards with homologous immunity did not contribute to virus transmission.
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http://dx.doi.org/10.1080/22221751.2020.1713706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006783PMC
September 2020

Experimental pigeon paramyxovirus-1 infection in chicken: evaluation of infectivity, clinical and pathological manifestations and diagnostic methods.

J Gen Virol 2020 02 10;101(2):156-167. Epub 2020 Jan 10.

Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.

Several pigeon paramyxovirus-1 (PPMV-1) outbreaks in feral pigeons were described recently in Switzerland. The potential of PPMV-1 to induce the notifiable Newcastle disease in chickens is discussed controversially. Therefore, in order to study epidemiologically relevant parameters such as the kinetics of PPMV-1 replication and shedding as well as seroconversion after infection, chickens were infected experimentally with a Swiss PPMV-1 isolate. This generated also defined sample material for the comparison of diagnostic tests. The infectivity of the Swiss PPMV-1 isolate for chickens was demonstrated successfully by virus shedding after experimental inoculation. Our data suggest that long-lasting shedding for up to 60 days can occur in chickens infected with PPMV-1. The isolate used here was of low pathogenicity for chickens. Different quantitative reverse transcription PCR assays were evaluated with a set of Swiss PPMV-1 isolates, and various samples from experimentally infected chickens were analysed with respect to their suitability for viral RNA detection. At 14 days post-infection, virus genome was detected mainly in spleen, caecal tonsils, heart, cloacal swabs, liver, proventriculus, duodenum and kidney tissue samples. Overall, the level of virus replication was low. Not all assays used routinely in diagnostics were capable of detecting viral genome from the isolates tested. Possible explanations are the genetic divergence of PPMV-1 and the low level of viral RNA in the samples. In contrast, two methods that are not used routinely proved more suitable for virus-genome detection. Importantly, the collection of material from various different organs is recommended, in addition to the kidney and brain analysed routinely. In conclusion, this study shows that there is a need to reconsider the type of samples and the protocols used for the detection of PPMV-1 RNA in chickens.
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http://dx.doi.org/10.1099/jgv.0.001364DOI Listing
February 2020

Genetic Characterization and Zoonotic Potential of Highly Pathogenic Avian Influenza Virus A(H5N6/H5N5), Germany, 2017-2018.

Emerg Infect Dis 2019 10;25(10):1973-1976

We genetically characterized highly pathogenic avian influenza virus A(H5N6) clade 2.3.4.4b isolates found in Germany in 2017-2018 and assessed pathogenicity of representative H5N5 and H5N6 viruses in ferrets. These viruses had low pathogenicity; however, continued characterization of related isolates is warranted because of their high potential for reassortment.
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http://dx.doi.org/10.3201/eid2510.181931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759249PMC
October 2019

Updated unified phylogenetic classification system and revised nomenclature for Newcastle disease virus.

Infect Genet Evol 2019 10 11;74:103917. Epub 2019 Jun 11.

Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, United Kingdom.

Several Avian paramyxoviruses 1 (synonymous with Newcastle disease virus or NDV, used hereafter) classification systems have been proposed for strain identification and differentiation. These systems pioneered classification efforts; however, they were based on different approaches and lacked objective criteria for the differentiation of isolates. These differences have created discrepancies among systems, rendering discussions and comparisons across studies difficult. Although a system that used objective classification criteria was proposed by Diel and co-workers in 2012, the ample worldwide circulation and constant evolution of NDV, and utilization of only some of the criteria, led to identical naming and/or incorrect assigning of new sub/genotypes. To address these issues, an international consortium of experts was convened to undertake in-depth analyses of NDV genetic diversity. This consortium generated curated, up-to-date, complete fusion gene class I and class II datasets of all known NDV for public use, performed comprehensive phylogenetic neighbor-Joining, maximum-likelihood, Bayesian and nucleotide distance analyses, and compared these inference methods. An updated NDV classification and nomenclature system that incorporates phylogenetic topology, genetic distances, branch support, and epidemiological independence was developed. This new consensus system maintains two NDV classes and existing genotypes, identifies three new class II genotypes, and reduces the number of sub-genotypes. In order to track the ancestry of viruses, a dichotomous naming system for designating sub-genotypes was introduced. In addition, a pilot dataset and sub-trees rooting guidelines for rapid preliminary genotype identification of new isolates are provided. Guidelines for sequence dataset curation and phylogenetic inference, and a detailed comparison between the updated and previous systems are included. To increase the speed of phylogenetic inference and ensure consistency between laboratories, detailed guidelines for the use of a supercomputer are also provided. The proposed unified classification system will facilitate future studies of NDV evolution and epidemiology, and comparison of results obtained across the world.
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http://dx.doi.org/10.1016/j.meegid.2019.103917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876278PMC
October 2019

Investigation of suspected Newcastle disease (ND) outbreaks in Egypt uncovers a high virus velogenic ND virus burden in small-scale holdings and the presence of multiple pathogens.

Avian Pathol 2019 Oct 25;48(5):406-415. Epub 2019 Jul 25.

Institute of Diagnostic Virology; Friedrich Loeffler-Institut , Greifswald - Insel Riems , Germany.

Highly contagious Newcastle disease (ND) is associated with devastating outbreaks with highly variable clinical signs among gallinaceous birds. In this study we aimed to verify clinical ND suspicions in poultry holdings in Egypt suffering from respiratory distress and elevated mortality, comparing two groups of ND-vaccinated poultry holdings in three governorates. Besides testing for Newcastle disease virus (NDV), samples were screened for infectious bronchitis virus (IBV) and avian influenza virus (AIV) by RT-qPCR as well as by non-directed cell-culture approach on LMH-cells. Virulent NDV was confirmed only in group A ( = 16) comprising small-scale holdings. Phylogenetic analysis of the fusion protein gene of 11 NDV-positive samples obtained from this group assigned all viruses to genotype 2.VIIb and point to four different virus populations that were circulating at the same time in one governorate, indicating independent epidemiological events. In group B, comprising large commercial broiler farms ( = 10), virulent NDV was not present, although in six farms NDV vaccine-type virus (genotype 2.II) was detected. Besides, in both groups, co-infections by IBV ( = 10), AIV H9 ( = 3) and/or avian reovirus (ARV) ( = 5) and avian astrovirus (AastVs) ( = 1) could be identified. Taken together, the study confirmed clinical ND suspicion in small scale holdings, pointing to inefficient vaccination practices in this group A. However, it also highlighted that, even in an endemic situation like ND in Egypt, in cases of suspected ND vaccine failure, clinical ND suspicion has to be verified by pathotype-specific diagnostic tests. Velogenic NDV circulates in small-scale poultry holdings in Egypt. Viral transmission occurred among neighbouring farms and over long distances. Co-infections with multiple pathogens were identified. Pathotype specific diagnostic tests are essential to verify ND suspicions.
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http://dx.doi.org/10.1080/03079457.2019.1612852DOI Listing
October 2019

A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential.

Emerg Microbes Infect 2018 Jul 19;7(1):132. Epub 2018 Jul 19.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that spread rapidly in a huge and ongoing outbreak series in Europe and caused high mortality in waterfowl and domestic birds. HPAIV H5N8B showed increased virulence with rapid onset of severe disease and mortality in Pekin ducks due to pronounced neuro- and hepatotropism. Cross-species infection was evaluated in mice, ferrets, and in a human lung explant culture model. While the H5N8B isolate was highly virulent for Balb/c mice, virulence and transmissibility were grossly reduced in ferrets, which was mirrored by marginal replication in human lung cultures infected ex vivo. Our data indicate that the 2016 HPAIV H5N8B is avian-adapted with augmented virulence for waterfowl, but has low zoonotic potential. The here tested combination of animal studies with the inoculation of human explants provides a promising future workflow to evaluate zoonotic potential, mammalian replication competence and avian virulence of HPAIV.
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http://dx.doi.org/10.1038/s41426-018-0130-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053424PMC
July 2018

From low to high pathogenicity-Characterization of H7N7 avian influenza viruses in two epidemiologically linked outbreaks.

Transbound Emerg Dis 2018 Dec 23;65(6):1576-1587. Epub 2018 May 23.

Friedrich-Loeffler-Institut, Greifswald, Germany.

The ability of low pathogenic (LP) avian influenza viruses (AIV) of the subtypes H5 and H7 to mutate spontaneously to highly pathogenic (HP) variants is the main reason for their stringent control. On-the-spot evidence from the field of mutations in LPAIV to render the virus into nascent HP variants is scarce. Epidemiological investigations and molecular characterization of two spatiotemporally linked outbreaks caused by LP, and subsequently, HPAIV H7N7 in two-layer farms in Germany yielded such evidence. The outbreaks occurred within 45 days on farms 400 m apart. The LP progenitor virus was identified on both farms, with its putative HP inheritor cocirculating and then dominating on the second farm. As postulated before, mutations in the hemagglutinin cleavage site (HACS) proved to be the most decisive change in the genome of HPAIV, in this case, it was mutated from monobasic (LP) PEIPKGR*GLF into polybasic (HP) PEIPKRKRR*GLF. The full-length genome sequences of both viruses were nearly identical with only ten coding mutations outside the HACS scattered along six genome segments in the HPAIV. Five of these were already present as minor variants in the LPAIV quasispecies of the LPAI-only affected farm. H7-specific seroconversion of part of the chicken population together with the codetection of LPAIV HACS sequences in swab samples of the HPAI outbreak farm suggested an initial introduction of the LP progenitor and a subsequent switch to HPAIV H7N7 after the incursion. The findings provide rare field evidence for a shift in pathogenicity of a notifiable AIV infection and re-inforce the validity of current approaches of control measures to curtail low pathogenic H5 and H7 virus circulation in poultry.
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http://dx.doi.org/10.1111/tbed.12906DOI Listing
December 2018

Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4b in Germany in 2016/2017.

Front Vet Sci 2017 24;4:240. Epub 2018 Jan 24.

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.

Here, we report on the occurrence of highly pathogenic avian influenza (HPAI) H5Nx clade 2.3.4.4b in Germany. Between November 8, 2016, and September 30, 2017, more than 1,150 cases of HPAI H5Nx clade 2.3.4.4b in wild birds and 107 outbreaks in birds kept in captivity (92 poultry holdings and 15 zoos/animal parks) were reported in Germany. This HPAI epidemic is the most severe recorded in Germany so far. The viruses were apparently introduced by migratory birds, sparking an epidemic among wild birds across Germany with occasional incursions into poultry holdings, zoos and animal parks, which were usually rapidly detected and controlled by stamping out. HPAI viruses (mainly subtype H5N8, in a few cases also H5N5) were found in dead wild birds of at least 53 species. The affected wild birds were water birds (including gulls, storks, herons, and cormorants) and scavenging birds (birds of prey, owls, and crows). In a number of cases, substantial gaps in farm biosecurity may have eased virus entry into the holdings. In a second wave of the epidemic starting from February 2017, there was epidemiological and molecular evidence for virus transmission of the infections between commercial turkey holdings in an area of high poultry density, which caused approximately 25% of the total number of outbreaks in poultry. Biosecurity measures in poultry holdings should be adapted. This includes, , wearing of stable-specific protective clothing and footwear, cleaning, and disinfection of equipment that has been in contact with birds and prevention of contacts between poultry and wild water birds.
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http://dx.doi.org/10.3389/fvets.2017.00240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787777PMC
January 2018

Zoonotic Infection With Pigeon Paramyxovirus Type 1 Linked to Fatal Pneumonia.

J Infect Dis 2018 08;218(7):1037-1044

Department of Viroscience, Erasmus University Medical Centre, Rotterdam, The Netherlands.

The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological, and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with PPMV-1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naive pigeons. Both patients were likely infected by contact with infected pigeons or doves. Given the large populations of feral pigeons with PPMV-1 infection in cities, increasing urbanization, and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend testing for avian paramyxovirus type 1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified.
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http://dx.doi.org/10.1093/infdis/jiy036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107406PMC
August 2018

Engineered recombinant protein products of the avian paramyxovirus type-1 nucleocapsid and phosphoprotein genes for serological diagnosis.

Virol J 2018 01 11;15(1). Epub 2018 Jan 11.

The Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Institute of Diagnostic Virology, Suedufer 10, 17493, Greifswald, Germany.

Background: Virulent Newcastle disease virus (NDV, avian Avulavirus-1, APMV-1) induces a highly contagious and lethal systemic disease in gallinaceous poultry. APMV-1 antibody detection is used for surveillance and to control vaccination, but is hampered by cross-reactivity to other subtypes of avian Avulaviruses. Data are lacking concerning the applicability of NDV V proteins as differential diagnostic marker to distinguish vaccinated from virus-infected birds (DIVA strategy).

Methods: Full length and C-terminally truncated nucleocapsid (NP) protein, and the unique C-terminal regions of the phospho- (P) and V proteins of the NDV LaSota strain were bacterially expressed as fusion proteins with the multimerization domain of the human C4 binding protein, and used as diagnostic antigens in indirect ELISA.

Results: When used as diagnostic antigen in indirect ELISAs, recombinant full-length proved to be a sensitive target to detect seroconversion in chickens after APMV-1 vaccination and infection, but revealed some degree of cross reactivity with sera raised against other APMV subtypes. Cross reactivity was abolished but also sensitivity decreased when employing a C-terminal fragment of the NP of NDV as diagnostic antigen. Antibodies to the NDV V protein were mounted in poultry following NDV infection but also, albeit at lower rates and titers, after vaccination with attenuated NDV vaccines. V-specific seroconversion within the flock was incomplete and titers in individual bird transient.

Conclusions: Indirect ELISA based on bacterially expressed recombinant full-length NP compared favorably with a commercial NDV ELISA based on whole virus antigen, but cross reactivity between the NP proteins of different APMV subtypes could compromise specificity. However, specificity increased when using a less conserved C-terminal fragment of NP instead. Moreover, a serological DIVA strategy built on the NDV V protein was not feasible due to reduced immunogenicity of the V protein and frequent use of live-attenuated NDV vaccines.
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http://dx.doi.org/10.1186/s12985-018-0924-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765633PMC
January 2018

Swarm incursions of reassortants of highly pathogenic avian influenza virus strains H5N8 and H5N5, clade 2.3.4.4b, Germany, winter 2016/17.

Sci Rep 2018 01 8;8(1):15. Epub 2018 Jan 8.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald-Insel, Riems, Germany.

The outbreak of highly pathogenic avian influenza H5Nx viruses in winter 2016/2017 was the most severe HPAI epizootic ever reported in Germany. The H5N8 and H5N5 viruses detected in birds in Germany in 2016/2017 represent a reassortant swarm of at least five distinct genotypes, which carried closely related HA segments derived from clade 2.3.4.4b. The genotypes of these viruses and their spatio-temporal distribution indicated a unique situation with multiple independent entries of HPAIV into Germany.
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http://dx.doi.org/10.1038/s41598-017-16936-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758748PMC
January 2018

Natural Reassortants of Potentially Zoonotic Avian Influenza Viruses H5N1 and H9N2 from Egypt Display Distinct Pathogenic Phenotypes in Experimentally Infected Chickens and Ferrets.

J Virol 2017 12 14;91(23). Epub 2017 Nov 14.

The Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Greifswald Insel-Riems, Germany

The cocirculation of zoonotic highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 and avian influenza virus (AIV) of subtype H9N2 among poultry in Egypt for at least 6 years should render that country a hypothetical hot spot for the emergence of reassortant, phenotypically altered viruses, yet no reassortants have been detected in Egypt. The present investigations proved that reassortants of the Egyptian H5N1 clade 2.2.1.2 virus and H9N2 virus of the G1-B lineage can be generated by coamplification in embryonated chicken eggs. Reassortants were restricted to the H5N1 subtype and acquired between two and all six of the internal segments of the H9N2 virus. Five selected plaque-purified reassortant clones expressed a broad phenotypic spectrum both and Two groups of reassortants were characterized to have retarded growth characteristics compared to the H5N1 parent virus. One clone provoked reduced mortality in inoculated chickens, although the characteristics of a highly pathogenic phenotype were retained. Enhanced zoonotic properties were not predicted for any of these clones, and this prediction was confirmed by ferret inoculation experiments: neither the H5N1 parent virus nor two selected clones induced severe clinical symptoms or were transmitted to sentinel ferrets by contact. While the emergence of reassortants of Egyptian HPAIV of subtype H5N1 with internal gene segments of cocirculating H9N2 viruses is possible in principle, the spread of such viruses is expected to be governed by their fitness to outcompete the parental viruses in the field. The eventual spread of attenuated phenotypes, however, would negatively impact syndrome surveillance on poultry farms and might foster enzootic virus circulation. Despite almost 6 years of the continuous cocirculation of highly pathogenic avian influenza virus H5N1 and avian influenza virus H9N2 in poultry in Egypt, no reassortants of the two subtypes have been reported. Here, the principal compatibility of the two subtypes is shown by forcing the reassortment between copassaged H5N1 und H9N2 viruses in embryonated chicken eggs. The resulting reassortant viruses displayed a wide range of pathogenicity including attenuated phenotypes in chickens, but did not show enhanced zoonotic propensities in the ferret model.
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http://dx.doi.org/10.1128/JVI.01300-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686759PMC
December 2017

Newcastle disease virus mediates pancreatic tumor rejection via NK cell activation and prevents cancer relapse by prompting adaptive immunity.

Int J Cancer 2017 12 13;141(12):2505-2516. Epub 2017 Sep 13.

Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.

Pancreatic cancer is the 8th most common cause of cancer-related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957, it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngeneic orthotopic tumor model using two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed. A single treatment with NDV inhibited DT6606PDA tumor growth in mice and prevented recurrence for a period of three months. Tumor infiltration and systemic activation of NK cells, cytotoxic and helper T-cells was enhanced. NDV-induced melting of Panc02 tumors until d7 pi, but they recurred displaying unrestricted tumor growth, low immunogenicity and inhibition of tumor-specific immune response. Arrest of DT6606PDA tumor growth and rejection was mediated by activation of NK cells and a specific antitumor immune response via T-cells. Panc02 tumors rapidly decreased until d7 pi, but henceforth tumors characterized by the ability to perform immune-regulatory functions reappeared. Our results demonstrated that NDV-activated immune cells are able to reject tumors provided that an adaptive antitumor immune response can be initiated. However, activated NK cells that are abundant in Panc02 tumors lead to outgrowth of nonimmunogenic tumor cells with inhibitory properties. Our study emphasizes the importance of an adaptive immune response, which is initiated by NDV to mediate long-term tumor surveillance in addition to direct oncolysis.
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http://dx.doi.org/10.1002/ijc.31026DOI Listing
December 2017

Heterologous post-infection immunity against Egyptian avian influenza virus (AIV) H9N2 modulates the course of subsequent infection by highly pathogenic AIV H5N1, but vaccination immunity does not.

J Gen Virol 2017 Jun 8;98(6):1169-1173. Epub 2017 Jun 8.

The Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald Insel-Riems 17493, Germany.

In Egypt, zoonotic A/goose/Guangdong/1/96 (gs/GD-like) highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1.2 is entrenched in poultry populations and has co-circulated with low-pathogenic avian influenza virus H9N2 of the G1 lineage since 2010. Here, the impact of H9N2 infection or vaccination on the course of consecutive infection with a lethal Egyptian HPAIV H5N1 is studied. Three-week-old chickens were infected with H9N2 or vaccinated with inactivated H9N2 or H5N1 antigens and challenged three weeks later by an HPAIV H5N1. Interestingly, pre-infection of chickens with H9N2 decreased the oral excretion of H5N1 to levels that were comparable to those of H5N1-immunized chickens, but vaccination with inactivated H9N2 did not. H9N2 pre-infection modulated but did not conceal clinical disease by HPAIV H5N1. By contrast, homologous H5 vaccination abolished clinical syndromic surveillance, although vaccinated clinical healthy birds were capable of spreading the virus.
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http://dx.doi.org/10.1099/jgv.0.000767DOI Listing
June 2017

New real time and conventional RT-PCRs for updated molecular diagnosis of infectious bronchitis virus infection (IBV) in chickens in Egypt associated with frequent co-infections with avian influenza and Newcastle Disease viruses.

J Virol Methods 2017 07 21;245:19-27. Epub 2017 Mar 21.

The Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald Insel-Riems 17493, Germany. Electronic address:

In Egypt, currently two geographically restricted genotypes of the infectious bronchitis coronavirus (IBV) are circulating with detrimental effects for poultry industry. A sensitive real-time RT-PCR assay targeting the IBV nucleocapsid gene (N) was developed to screen clinical samples for presence of IBV. Conventional RT-PCRs amplifying hypervariable regions (HVRs 1-2 and 3) of the IBV S1 gene were developed and amplificates used for nucleotide sequence-based typing of IBV field strains in Egyptian chickens directly from clinical samples.
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http://dx.doi.org/10.1016/j.jviromet.2017.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113857PMC
July 2017

Outbreaks among Wild Birds and Domestic Poultry Caused by Reassorted Influenza A(H5N8) Clade 2.3.4.4 Viruses, Germany, 2016.

Emerg Infect Dis 2017 04 15;23(4):633-636. Epub 2017 Apr 15.

In November 2016, an influenza A(H5N8) outbreak caused deaths of wild birds and domestic poultry in Germany. Clade 2.3.4.4 virus was closely related to viruses detected at the Russia-Mongolia border in 2016 but had new polymerase acidic and nucleoprotein segments. These new strains may be more efficiently transmitted to and shed by birds.
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http://dx.doi.org/10.3201/eid2304.161949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367393PMC
April 2017

Highly pathogenic avian influenza A(H5N8) outbreaks: protection and management of exposed people in Europe, 2014/15 and 2016.

Euro Surveill 2016 Dec;21(49)

European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.

Introduction of highly pathogenic avian influenza (HPAI) virus A(H5N8) into Europe prompted animal and human health experts to implement protective measures to prevent transmission to humans. We describe the situation in 2016 and list public health measures and recommendations in place. We summarise critical interfaces identified during the A(H5N1) and A(H5N8) outbreaks in 2014/15. Rapid exchange of information between the animal and human health sectors is critical for a timely, effective and efficient response.
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http://dx.doi.org/10.2807/1560-7917.ES.2016.21.49.30419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291128PMC
December 2016