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United States Department of Agriculture

Agricultural Research Service

Research Project: NEWCASTLE DISEASE EPIDEMIOLOGY, PATHOGENESIS, AND CONTROL Title: Construction of recombinant Newcastle disease viruses expessing chicken IFN-gamma: effect of elevated levels of expression on the transcriptional host response, viral replication and pathogenesis

Authors
item Susta, Leonardo -
item Edwards, Ingrid
item Cardenas, Stivalis -
item Miller, Patti
item Brown, Corrie -
item Afonso, Claudio

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: March 15, 2011
Publication Date: May 15, 2011
Citation: Susta, L., Edwards, I.C., Cardenas, S., Miller, P.J., Brown, C.C., Afonso, C.L. 2011. Construction of recombinant Newcastle disease viruses expessing chicken IFN-gamma: effect of elevated levels of expression on the transcriptional host response, viral replication and pathogenesis [abstract]. 1st International Avian Respiratory Disease Conference, May 15-18, 2011, Athens, Georgia. p. 15.

Technical Abstract: Newcastle disease (ND) is a severe problem of poultry and other avian species, characterized by high morbidity and mortality. It is caused by virulent strains of Newcastle disease virus (NDV), part of the Mononegavirales class, Paramyxoviride family, Avulavirus genus. Although it is one of the most important and widely distributed diseases of poultry in the world, little is known about the molecular pathogenesis of the disease. Some studies suggest that a cellular response from type 1 T helper cells (Th1) is important in viral clearance and resistance. In order to further characterize the role of the Th1 response during infection in the animal system, the open reading frame (ORF) of interferon gamma (IFN-gamma), a well known Th1-type cytokine, was inserted in the backbone of a recombinant virulent viscerotropic NDV isolate, rZJ1, between the phosphoprotein (P) and matrix (M) genes. The cytokine should be produced concomitantly with new virions in the cells of the host. The recombinant virus (rZJ1-IFN-gamma) had comparable growth titers to the backbone controls (rZJ1-GFP). Analysis of mean death time (MDT), intracerebral pathogenicity index (ICPI), and adult bird pathogenesis studies revealed that the ZJ1-IFN-gamma had markedly decreased virulence compared to the controls: a rZJ1 with no insertion and a rZJ1GFP, a recombinant with the green fluorescent protein inserted between the P and M genes. A revertant ZJ1-IFN-gamma in which IFN-gamma ORF was eliminated, was constructed to confirm that the attenuation was caused by expression of the IFN gene. Changes in cytokine messenger RNA (mRNA) expression of IFN-gamma, interleukin 2(IL-2), IL-6, IL-1Beta and IL-8 and the mRNA expression of inducible nitric oxide synthase in the spleen and the lung were measured by quantitative reverse transcription PCR. ZJ1-IFN-gamma induced significant up-regulation of IFN-gamma expression and prevented viral-induced down-regulation of IL-2 and IL-1Beta expression in both organs. These data suggest that early production of IFN-gamma could markedly decrease the severity of disease due to virulent strains.

Last Modified: 10/23/2014
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