The main role of the Administration Core is to evaluate and coordinate advances in the research among the three research projects and multiple institutions participating in the Center proposal. Project 1 will define the structural/biochemical basis for IFN-antagonist-host factor interactions and define the impact of these interactions on DC maturation and function. Project 2 will address the hypotheses that that the disrupted maturation of DCs induced by EBOV and MARV infection will lead to impaired T cell activation and aberrant/absent T cell function and that the mechanisms of the filoviral IFN-antagonist proteins make key contributions to these outcomes. Project 3 will characterize the phenotype and functional status of dendritic cells and lymphocytes during filovirus infection in vivo. These studies will be carried out at four different institutions by seven different laboratories. To ensure that the progress of this integrated research program will be maximized, the Administration Core (Core A) will be responsible for the following roles: Coordinate: weekly (at a minimum) teleconferences between the Pis of the research projects and cores;monthly (at a minimum) scheduled web-based interlab meetings to exchange and critique data;and an Annual Meeting among members of all participating groups and the Scientific Advisory Board (SAB) to assess scientific progress. These meetings will facilitate reagent and scientific exchanges between the different laboratories. It will also coordinate annual participation in the annual National IMVC Program meeting. In addition, the Administration will coordinate budget issues. It will assist the investigators with manuscript preparation and submission of annual progress reports to the NIH. It will also maintain a web site for data dissemination in connection with this project and facilitate data sharing and regulatory compliance. Core A will include an Administrator, hired specifically for this purpose and Dr. Thomas Moran, an accomplished viral immunologist with significant prior experience serving as PI of multi-investigator Center grants. Dr. Moran will provide advice to Dr. Basler who will serve as overall PI and supervisor or Core A.
Ebola viruses are important emerging and biodefense pathogens for which approved therapeutic approaches are lacking. The proposed characterization of immune evasion mechanisms and their contribution to pathogenesis will suggest new therapeutic strategies. The Administration Core will provide necessary support to maximize the productivity and interaction of the laboratories performing this work.
|Feagins, Alicia R; Basler, Christopher F (2014) The VP40 protein of Marburg virus exhibits impaired budding and increased sensitivity to human tetherin following mouse adaptation. J Virol 88:14440-50|
|Shabman, Reed S; Jabado, Omar J; Mire, Chad E et al. (2014) Deep sequencing identifies noncanonical editing of Ebola and Marburg virus RNAs in infected cells. MBio 5:e02011|
|Basler, Christopher F (2014) New hope in the search for Ebola virus treatments. Immunity 41:515-7|
|Xu, Wei; Edwards, Megan R; Borek, Dominika M et al. (2014) Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. Cell Host Microbe 16:187-200|
|Basler, Christopher F; Woo, Patrick C Y (2014) Editorial overview: emerging viruses. Curr Opin Virol 5:v-vii|
|Yen, Benjamin; Mulder, Lubbertus C F; Martinez, Osvaldo et al. (2014) Molecular basis for ebolavirus VP35 suppression of human dendritic cell maturation. J Virol 88:12500-10|
|Basler, Christopher F (2014) Portrait of a killer: genome of the 2014 EBOV outbreak strain. Cell Host Microbe 16:419-21|