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Mentor: Wendy Maury, PhD
Undergraduate Institution: University of St. Thomas
Year Entered Into Program: 2010-2011
Ebolavirus (EBOV) and Marburgvirus are enveloped, negative-sense, single-stranded RNA virus in the Filoviridae family. This family of viruses causes severe hemorrhagic fever in humans and non-human primates. The EBOV is composed of 5 different strains with Zaire EBOV (ZEBOV) being the most virulent. Until recently, a cellular receptor that interacts with EBOV glycoprotein (GP) to mediate Ebolavirus entry had remained elusive. An epithelial cellular receptor for filoviruses was identified to be T-Cell Immunoglobulin Mucin Domain 1 (TIM-1) (Kondratowicz et al. 2011). TIM-1 is one of three members of a family of cell surface proteins in humans (TIM-1, TIM-3 and TIM-4). Preliminary evidence indicates that TIM-4 also mediates filovirus entry. A TIM-4 expression plasmid was transfected into poorly permissive 293T cells that do not endogenously express any of the human TIM family members (Kondratowicz et al. 2011). Transfected cells were infected with replicating, GFP-expressing VSV that contained ZEBOV-GP (ZEBOV-GP/rVSV GFP) rather than the native glycoprotein VSVG. Expression of TIM-4 allowed efficient infection by ZEBOV-GP/rVSV GFP relative to cells transfected with an empty plasmid, indicating that TIM-4 enhances ZEBOV infection. The goal of my studies is to determine the importance of TIM-4 as a receptor for ZEBOV. Specifically, I am working to identify human TIM-4 IgV residues that are critical for Zaire-EBOV entry along with analyzing the interaction of ZEBOV-GP with wild-type and mutant TIM-4 IgV domains. Finally, I hope to determine the effect of TIM-4 on in vivo Zaire-EBOV infections utilizing a mouse model.
Fischer, A.J., N.J. Lennemann, S. Krishnamurthy, P. Pócza, L. Durairaj, J.L. Launspach, B.A. Rhein, C. Wohlford-Lenane, D. Lorentzen, B. Bánfi, P.B. McCray, Jr. Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. Am. J. Respir. Cell Mol. Biol. 2011 Oct; 45 (4):874-881. PubMed PMID: 21441383; PubMed Central PMCID: PMC3208616
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