Submitted to: Journal of General Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/21/2010
Publication Date: 3/1/2011
Citation: Rue, C.A., Susta, L., Edwards, I.C., Brown, C.C., Kapczynski, D.R., Suarez, D.L., King, D.J., Miller, P.J., Afonso, C.L. 2011. Virulent Newcastle disease virus elicits a strong innate immune response in chickens. Journal of General Virology. 92:931-939. Interpretive Summary: Current vaccines for Newcastle Disease Virus (NDV) prevent disease, but do not prevent virus replication or shedding. This likely contributes to periodic emergence of highly virulent strains. To be able to design rational recombinant vaccines, a better understanding of the host response to infection is necessary. We characterized the response of chickens to infection with a highly virulent NDV strain, California 2002. A strong host response was detected which included the induction of groups of genes involved in the anti-viral innate and pro-inflammatory response including interferons, interferon stimulated genes, nitric oxide synthase, and several pro-inflammatory cytokines. Nitric oxide, the product of inducible nitric oxide synthase (iNOS) was detected at elevated levels in serum of infected chickens, as well. This study provides much basic knowledge about the chicken’s response to NDV. This will serve as a foundation to future studies on the role of the immune response in Newcastle Disease required for future vaccine design.
Technical Abstract: Newcastle Disease Virus (NDV) is an avian paramyxovirus that has caused significant economic losses to the US poultry industry. Despite the fact that a live-attenuated vaccine has been used for decades, outbreaks of highly virulent strains still occur periodically. To create rationally-designed recombinant vaccines, a more thorough understanding of the host response to infection is required. There is limited knowledge about the avian response to paramyxoviruses, and how this response may contribute to disease. In this study, the early host response to a recent NDV outbreak strain of high virulence is characterized in vivo using microarray. A strong host response is observed with groups of genes involved in innate anti-viral and pro-inflammatory responses being significantly induced. Among these are numerous interferons, cytokines, chemokines, interferon effectors and inducible nitric oxide synthase, and high levels of nitric oxide were detected in serum of infected birds at days 2 and 3 post-inoculation. In vitro experiments showed induction of key host response genes, interferons alpha and beta and interleukins 1beta and 6, in splenic lymphocytes at 6 hours post-infection, as well. The robust host response to NDV shown here, and the rapid mortality of this outbreak strain, provide evidence that the host response itself may significantly contribute to disease.