Title: Expression of interferon gamma by a highly virulent Newcastle disease virus decreases its pathogenicity in chickens Authors
|Cornax, Ingrid -|
|Cardenas, Stivalis Garcia -|
|Brown, Corrie -|
Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 16, 2013
Publication Date: May 25, 2013
Citation: Susta, L., Cornax, I., Diel, D.G., Cardenas, S., Miller, P.J., Brown, C.C., Afonso, C.L. 2013. Expression of interferon gamma by a highly virulent Newcastle disease virus decreases its pathogenicity in chickens. Microbial Pathogenesis. 62:73-83. Interpretive Summary: Newcastle disease (ND) is a severe disease of all birds, including chickens and turkeys, causing high rates of death. Chicken interferon-gamma (IFN-g) is a substance produced by the chicken after it is infected with Newcastle disease virus (NDV). This substance is produced to prevent the virus from growing in the body of the bird. In this paper, we describe the creation and characterization of recombinant NDV that was made to produce chicken IFN-g as the virus grows and replicates in the host. The NDV that was used is a highly lethal strain of NDV named ZJ1. We inserted the chicken IFN-g gene into ZJ1 genome. The resulting recombinant virus (rZJ1-IFNg) was compared with the same virus with green fluorescent protein (GFP) gene inserted at an identical position (rZJ1-GFP). The GFP is acting as a control since the expression of GFP should not decrease the virulence of the ZJ1 virus. We also compared it to rZJ1-Rev; the same virus that contains the chicken IFN-g but lacks the part necessary for the substance to be produced. The three viruses were compared to see how they would grow in cell culture. They were also given to chickens to test their virulence/rates of death. Results showed that rZJ1-IFNg grew at the same rate than controls on cell cultures, and was able to produce chicken IFNg. In addition, rZJ1-IFNg caused markedly less death in chickens compared to the two controls, and the ability to cause lesions was slightly decreased. The data suggest that chicken IFN-g gene inserted into NDV virus is sufficient to make NDV less lethal. Finally we suggest that NDV may be effectively used to deliver chicken IFN-g into different organs of the avian system as a way to control the disease.
Technical Abstract: Infection of chickens with highly virulent NDV results in rapid death, which is preceded by increased expression of interferon gamma (IFN-g) in target tissues. IFN-g is a cytokine that has pleiotropic biological effects including intrinsic antiviral activity and immunomodulatory effects. Here we assessed the effects of IFN-g on NDV pathogenesis in chickens. For this, the coding sequence of chicken interferon gamma was inserted in the genome of the highly virulent NDV strain ZJ1 (rZJ1-IFNg), and the effects of IFN-g expression were determined in vivo by comparing the pathogenesis of rZJ1-IFNg with a control virus expressing the green fluorescent protein (rZJ1-GFP). Expression of IFN-g decreased the intra cerebral pathogenicity index (ICPI) of rZJ1-IFNg, when compared to the control rZJ1-GFP. Additionally rZJ1-IFNg presented a marked decrease in pathogenicity in 4-week-old chickens, as evidenced by lower mortality rates, decreased disease severity, viral shedding, and antigen distribution. These results suggest that early expression of IFN-g during viral replication has a protective effect against virulent NDV infection in chickens, and further suggests that the level and time of expression of IFN-g are critical for the disease outcome.