The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

Other endocytic mechanisms used by viruses have been identified (Mercer et al., 2010b) . Less is known about the molecular mechanisms and receptors involved or whether these pathways are constitutively active or driven by receptor engagement. One such example is the pathway used by the polyomavirus SV40. This nonenveloped virus measures only 40 nm in diameter and exhibits a penetration mechanism that is currently unique to some polyomaviruses. SV40 particles bind directly to the cell surface via the sialic acid moieties of GM1 gangliosides, for which there are 360 binding sites on the virion surface (Stehle et al., 1994) . Aggregation of GM1 by multivalent particles results in lipid phase separation and the induction of membrane deformation (Ewers et al., 2010) . These two properties drive SV40 particles into tightly fitting membrane tubules that extend into the cell interior. Membrane tubulation is dependent on the long acyl chains of GM1 but is independent of cellular energy (Ewers et al., 2010) . Subsequent scission of these invaginations requires tyrosine kinase activity and actin rearrangements (Pelkmans et al., 2002; Ewers et al., 2010; Römer et al., 2010) . It has been suggested that caveolae coat proteins and dynamin are also recruited (Pelkmans et al., 2001 (Pelkmans et al., , 2002 ; however, other studies indicate that Cav-1 is not essential for SV40 infection (Damm et al., 2005; Ewers et al., 2010) . Interestingly, membrane deformation by SV40 has parallels with the endocytosis of shiga and cholera toxins (Römer et al., 2007 . Although there is no sequence homology, similar pentameric ganglioside binding sites on SV40 and the two toxins, in conjunction with the rigid structure of the long-chained glycosphingolipids, appear to induce asymmetric compressive stress that promotes local membrane tubulation (Neu et al., 2010) . Some related polyomaviruses also induce tubulation and may share a common route of internalization (Ewers et al., 2010) .