The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

The filamentous particles of Ebola virus have a diameter of only 80-100 nm but range from 1-2 µm in length. It is not surprising that these viruses also induce macropinocytosis through Rac-1/Pak-1-dependent membrane ruffling. Although the role of the putative Ebola virus receptor TIM-1 in macropinocytosis is unclear, Ebola virus uptake is promoted by the receptor tyrosine kinase Axl. The virus particle is not thought to directly engage Axl; however, Gas-6, an Axl ligand, has been For clathrin-mediated endocytosis, at least, influenza A virus attachment to sialic acid moieties on membrane glycoproteins and ganglioside initiates de novo clathrin-coated pit formation under surface-bound virions in a process that appears to involve ubiquitin-dependent recruitment of the clathrin adaptor protein Epsin-1 (Rust et al., 2004; Chen and Zhuang, 2008 ). An independent study has demonstrated that activation of PI3K, but not Akt, is required for influenza A virus entry, and inhibition of PI3K prevents virus uptake into endosomes (Ehrhardt et al., 2006) . It is proposed that influenza A virus-mediated clustering of sialylated receptor tyrosine kinases, such as EGFR or c-Met, activates tyrosine kinase and PI3K signaling (Eierhoff et al., 2010) . However, it remains unclear whether this signal propagation is linked to virus internalization by a clathrin-dependent or -independent route. Virus-induced receptor clustering also seems to be important for signaling-dependent DC-SIGNmediated infection of phleboviruses (Lozach et al., 2011b) .