Filovirus Tropism: Cellular Molecules for Viral Entry

Takada, Ayato

infect T-cell lines stably expressing this protein, suggesting that folate receptor-α is not sufficient to mediate entry (i.e., some other molecules are required) (Simmons et al., 2003b; Sinn et al., 2003) . A similar approach identified members of the Tyro3 receptor tyrosine kinase family (Axl, Dtk, and Mer) as molecules involved in cell entry of filoviruses (Shimojima et al., 2006) . Expression of these family members in lymphoid cells, which are originally non-permissive to filoviruses, enhanced infection by pseudotype viruses bearing filovirus GPs on their envelopes. These molecules are widely distributed in many types of cells throughout the body, though not on lymphocytes and granulocytes (Linger et al., 2008) . A more recent study demonstrated that reduction of Axl expression by RNAi treatment resulted in decreased ZEBOV entry via. macropinocytosis but had no effect on the clathrin-dependent or caveola/lipid raft-mediated endocytic mechanisms, suggesting that Axl enhances macropinocytosis . However, direct interactions between these cellular molecules and the GP RBR remain to be demonstrated.