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Title: Evaluation of different hemagglutinin-neuraminidase and fusion protein chimeras using a reverse genetic system based on the mesogenic anhinga Newcastle disease virus strain

Author
item Estevez, Carlos
item King, Daniel
item Miller, Patti
item Yu, Qingzhong

Submitted to: World Veterinary Poultry Association
Publication Type: Proceedings
Publication Acceptance Date: 8/15/2007
Publication Date: 9/14/2007
Citation: Estevez, C., King, D.J., Miller, P.J., Yu, Q. 2007. Evaluation of different hemagglutinin-neuraminidase and fusion protein chimeras using a reverse genetic system based on the mesogenic anhinga Newcastle disease virus strain. In: The 15th World Poultry Veterinarian Association Abstract Book, September 10-15, 2007, Beijing, China. p. 153.

Interpretive Summary:

Technical Abstract: Introduction: Newcastle disease (ND) is one of the most serious infectious diseases of poultry, and virulent ND outbreaks require reporting to the World Organization for Animal Health (OIE). Newcastle disease virus (NDV), the causative agent of ND, is a non-segmented, single-stranded, negative sense RNA virus of the genus Avulavirus in the Paramyxovirinae subfamily of the Paramyxoviridae family. All known strains of the virus are of a single serotype, but are classically defined as members of one of three pathotypes: lentogenic, mesogenic, and velogenic, reflecting increasing levels of virulence. A major factor in the pathogenicity of NDV is the amino acid sequence of the fusion (F) protein cleavage site; but the role of other viral genes in the different clinical forms of the disease are incompletely defined. The purpose of this study was to evaluate the contribution of the hemagglutinin-neuraminidase (HN) and F proteins to the virus pathotype. Methods: To assess the role of other NDV genes in virus pathogenicity, a reverse genetics system was established with the NDV anhinga strain, a virus of moderate virulence, to provide a backbone for generating gene mutations or gene exchanges in attempts to enhance or attenuate virulence of that virus. Recombinant viruses coding for the HN and F proteins (alone or in combination) of the neurotropic Turkey/U.S.(ND)/43084/92 (TkND) or the viscerotropic velogenic game fowl/U.S.(CA)/211472/02 (CA02) NDV strains were generated by conventional molecular manipulation methods. The pathogenicity of these recombinants was assessed by performing the mean death time (MDT) in embryonated chicken eggs and intracerebral pathogenicity index (ICPI) in day-old susceptible chickens. Results/Discussion: These results indicated that the chimeras created by exchange of the Anhinga HN and F protein genes with HN and F genes of neurotropic and viscerotropic velogens slightly increased the ICPI and decreased the MDT, but they were still in the range of mesogenic pathotype according to the standard NDV pathotype definition. It’s concluded that a HN and F gene exchange within the context of the mesogenic NDV anhinga backbone failed to increase the recombinant virus pathotype from mesogenic to velogenic and suggests a multigenic role for NDV pathogenicity.