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Title: Retroviral delivery of RNA interference against Marek's disease virus in vivo

Author
item CHEN, MO
item PAYNE, WILLIAM
item Dunn, John
item CHANG, SHUANG
item Zhang, Huanmin
item Hunt, Henry
item DODGSON, J

Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/12/2009
Publication Date: 7/1/2009
Citation: Chen, M., Payne, W.S., Dunn, J.R., Chang, S., Zhang, H.M., Hunt, H.D., Dodgson, J.B. 2009. Retroviral Delivery of RNA Interference Against Marek's Disease Virus In Vivo. Poultry Science. 88(7):1373-1380.

Interpretive Summary: Marek’s disease is a cancer of chickens induced by the Marek’s disease virus (MDV). The diseases induced are, in part, due to their ability to evade the natural defense mechanisms of their host. Developing new strategies to induce host resistance is an important component needed to reduce the ability of viruses to evade host defense mechanisms and cause disease. This report describes how a natural system used to control gene expression called RNA interference or RNAi, was used to inhibit the replication of Marek’s disease virus, a cancer-causing virus of poultry, and to reduce disease in-vivo.

Technical Abstract: RNA interference (RNAi) has been used widely to modify plant phenotypes and has the potential to be used similarly in chickens. One phenotypic alteration of special interest would be to enhance resistance to avian viruses such as Marek’s Disease virus (MDV). We previously demonstrated that avian leukosis virus-based retroviral vectors are capable of delivering effective RNAi against MDV in cell culture. In this study, similar RNAi vectors are shown to reduce the replication of MDV in live chickens. Retroviral vectors were introduced into unincubated chick embryos, followed by incubation until hatching. Chicks were challenged with 500 pfu of strain 648A MDV at day of hatch, followed by assays for viremia, generally at 14 days post-infection. Birds were monitored for signs of Marek’s Disease for 8 weeks. A stem-loop PCR assay was developed to measure siRNA expression levels in birds. Delivery of RNAi co-targeting the MDV gB glycoprotein gene and ICP4 transcriptional regulatory gene significantly reduced MDV viremia in vivo, but not to the extent that we had previously observed in cell culture. Concomitant reductions in disease incidence also were observed, but the extent of this effect depended on the potency of the challenge virus inoculum. These reductions were statistically significant in some trials, but not in all cases. Successful modification of phenotypic traits in live birds with retroviral RNAi vectors opens up the possibility that such approaches could be used to alter the expression of candidate genes hypothesized to influence a variety of quantitative traits including disease susceptibility.