Filovirus Entry: A Novelty in the Viral Fusion World

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

The TAM family member Axl was first implicated in filovirus entry through a cDNA screen that introduced Vero E6 cell cDNA into poorly permissive Jurkat T cells [41] . Axl is a tyrosine kinase receptor that is found on the plasma membrane in a variety of different cell types and enhances cell migration, division and viability upon activation [58] . Shimojima et al. demonstrated that anti-Axl antibodies blocked EBOV transduction of some cells, whereas these antibodies had no effect on transduction of other cells [41] . Mapping studies indicated that amino acid residues in both the ectodomain and the cytoplasmic tail of Axl were required for filovirus entry enhancement [59] . Subsequently, a screen performed in our laboratory also identified Axl as being important in EBOV GP-dependent entry [60] . Through the use of multiple biochemical inhibitors, siRNA and anti-Axl antibodies, we defined a role for Axl in EBOV uptake [61] , demonstrating that Axl expression enhances macropinocytosis in some cells. As macropinocytosis is a principal uptake mechanism of filoviruses [62, 63] , increased Axl surface expression leads to greater virus internalization. However, Axl does not appear to interact directly with EBOV GP to promote viral internalization and therefore is unlikely to serve as a filoviral receptor [60] .