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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Complementation of the human adenovirus type 5 VA RNAI defect by the Vaccinia virus E3L protein and serotype-specific
Raviteja Inturi1, Wael Kamel1, Göran Akusjärvi1
1Department of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, BMC, Box 582, Uppsala, Sweden.
Abstract:
Human adenoviruses (HAdVs) encode for multifunctional non-coding virus-associated (VA) RNAs, which function as powerful suppressors of the cellular interferon (IFN) and RNA interference (RNAi) systems. In this study we tested the ability of various plant and animal virus encoded RNAi and IFN suppressor proteins to functionally substitute for the HAdV-5 VA RNAI. Our results revealed that only the Vaccinia virus (VACV) E3L protein was able to substitute for the HAdV-5 VA RNAI functions in virus-infected cells. Interestingly, the E3L protein rescues the translational defect but does not stimulate viral capsid mRNA accumulation observed with VA RNA. We further show that the E3L C-terminal region containing the dsRNA-binding domain is needed to enhance VA RNAI mutant virus replication. Additionally, we show that the HAdV-4 and HAdV-37 VA RNAI are more effective than the HAdV-5 VA RNAI in rescuing virus replication.
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