Filovirus Entry: A Novelty in the Viral Fusion World

Hunt, Catherine L.; Lennemann, Nicholas J.; Maury, Wendy

Our lab performed a comparative genomic analysis (CGA) screen [64] to identify cellular genes whose expression highly correlated with EBOV pseudovirion transduction [43] . This screen showed a positive correlation between EBOV transduction and expression of a series of cellular proteins that were previously appreciated to enhance EBOV transduction (C-type lectins, integrins and Axl). Interestingly, expression of the T-cell immunoglobulin mucin domain-1 (TIM-1) gene proved to be one of the strongest positive correlations. Subsequent studies demonstrated that expression of TIM-1 in poorly permissive cells enhanced EBOV entry and loss of surface-expressed TIM-1 in highly permissive cells abrogated filovirus infection/transduction. Furthermore, TIM-1 and the mucin domain-deleted EBOV GP interacted, and removal of the glycan cap enhanced the specificity of GP interaction with TIM-1-expressing cells [43] . In total, these findings have led us to propose TIM-1 as a cell surface receptor for filoviruses. As epithelial cells are the only relevant cell type that expresses TIM-1, it is likely that other as of yet unidentified surface receptors will also prove to be important in mediating filovirus entry.