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Title: Inhibition of Marek's disease virus replication by retroviral vector-based RNA interference

Author
item CHEN, MO - MICHIGAN STATE UNIVERSITY
item PAYNE, WILLIAM - MICHIGAN STATE UNIVERSITY
item Hunt, Henry
item Zhang, Huanmin
item HOLMEN, SHERI - NEVADA CANCER INSTITUTE
item DODGSON, JERRY - MICHIGAN STATE UNIVERSITY

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2008
Publication Date: 6/18/2008
Citation: Chen, M., Payne, W.S., Hunt, H.D., Zhang, H., Holmen, S.L., Dodgson, J.B. 2008. Inhibition of Marek's disease virus replication by retroviral vector-based RNA interference. Virology. 377:265-272.

Interpretive Summary: Marek’s disease (MD) is an important infectious disease of chicken caused by a herpesvirus (MDV). Presently, this virus is controlled by vaccines, however, new and improved controlled methods are needed as it is well-documented that MDV can evolve to greater virulence. In this report, we describe how a natural system in the host used to control gene expression called RNA interference or RNAi was engineered to inhibit the replication of MDV. If successfully transferred to the commercial environment, this tool will provide a safe, efficient, and economical method to control MD and other infectious diseases in poultry.

Technical Abstract: RNA interference (RNAi) is a promising antiviral methodology. We recently demonstrated that retroviral vectors expressing short hairpin RNAs (shRNA-mirs) in the context of a modified endogenous micro-RNA (miRNA) can be effective in reducing replication of other retroviruses in chicken cells. In this study, similar RNAi vectors are shown to inhibit replication of the avian herpesvirus, Marek’s disease virus (MDV), and its close relative, herpesvirus of turkeys (HVT). Cells expressing shRNA-mirs targeting the MDV or HVT gB glycoprotein gene or the ICP4 transcriptional regulator gene show significant inhibition of viral replication. Not only are viral titers reduced, but observed plaque sizes are significantly smaller when the virus is grown on cells in which RNAi is effective. We also describe a modified retroviral delivery vector that expresses a shRNA-mir containing up to three RNAi target sequences and present results using this vector with multiple targets within the MDV gB gene or within both the gB and ICP4 genes. This multi-target vector may be valuable for eventual in vivo applications in reducing possible escape mutations in the target virus.