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Title: Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens

item SUSTA, LEONARDO - University Of Guelph
item DIEL, DIEGO - South Dakota State University
item COURTNEY, SEAN - University Of Georgia
item CARDENAS-GARCIA, STIVALIS - University Of Georgia
item SUNDICK, ROY - Wayne State University
item Miller, Patti
item BROWN, CORRIE - University Of Georgia
item Afonso, Claudio

Submitted to: Virology Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/28/2015
Publication Date: 8/8/2015
Citation: Susta, L., Diel, D., Courtney, S., Cardenas-Garcia, S., Sundick, R., Miller, P.J., Brown, C., Afonso, C.L. 2015. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens. Virology Journal. 12:122. DOI: 10.1186/s12985-015-0353-x.

Interpretive Summary: Virulent Newcastle disease viruses can replicate in vaccinated poultry. Therefore, there is strong interest in developing improved NDV vaccines capable of reducing replication of challenge viruses. Recently, it has been shown that interleukin-2 (IL-2) delivered by a live virus vaccine vector can improve the effectiveness of co-administered vaccines. In order to determine the suitability of the chicken IL-2 protein as an adjuvant, we created Newcastle disease viruses that express high levels of IL-2. Our work demonstrates that IL-2 expression by Newcastle disease virus did not significantly affect the mortality caused by the virus nor did it prevent its own replication. Furthermore, our work demonstrated that NDV can effectively deliver IL-2.

Technical Abstract: In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens by activating natural killer cells (NK), cytotoxic T lymphocytes, and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such it might have the potential to affect replication and pathogenesis of Newcastle disease virus (NDV). To assess the role of IL-2 on NDV pathogenesis, we produced a recombinant virulent NDV strain expressing chicken IL-2 (rZJ1-IL2). The effects of IL-2 expression were investigated in vivo by comparing the pathogenesis of rZJ1-IL2 to a control virus expressing the green fluorescent protein (rZJ1-GFP). Expression of IL-2 did not affect the pathogenicity of rZJ1-IL2 when inoculated intracranially into day-old chicks, compared to rZJ1-GFP strain. Four week-old chickens infected with rZJ1-IL2 via eyelid installation presented survival curves similar to control birds infected with rZJ1-GFP, with comparable clinical signs and 100% mortality. However, compared to rZJ1-GFP-, rZJ1-IL2-infected birds had decreased severity and distribution of lesions, with decreased viral load in blood, spleen, and mucosal secretions. In the rZJ1-IL2-infected group, viremia peaked at day 4 post infection [10^(3.46) EID50/0.1 ml of blood] and drastically decreased at day 5 post infection [10^(0.9) EID50/0.1 ml], while in the rZJ1-GFP-infected group viremia reached 10^(5.35) EID50/0.1 ml of blood at day 5, suggesting that IL-2 might have some negative impact on NDV replication. In addition, these results demonstrate that NDV can effectively deliver IL-2, and this might warrant the use of low virulence NDV strains expressing IL-2 as co-administered vaccines.