The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

Endocytosis provides a mechanism through which viruses can pass through the cortex by exploiting intrinsic properties of endocytic vesicles to migrate (Fig. 1 A) . The requirement for exposure to low pH, lysosomal enzymes, or even the reducing environment of the ER (see below) by many viruses ensures that they are captured by endocytic vesicles before undergoing the fusion/penetration reactions that allow them to transit the membrane barrier (Fig. 3) . Recent system-based approaches have identified several endocytic mechanisms, either constitutively active or induced, that viruses can exploit (Mercer et al., 2010b) . One obvious feature of this endocytic involvement is that virus size tends to influence the mechanism of uptake. Thus, small viruses (approximately <140 nm in diameter) tend to use small endocytic vesicles. The best characterized of these is the clathrin-mediated pathway that is essential for productive infection by many viruses. Initially demonstrated for the alphavirus Semliki Forest virus Marsh and Helenius, 1980) , a more recent study shows, for example, that human rhinovirus 2 is internalized via the constitutive clathrin-mediated endocytosis of its receptor LDLR (Snyers (B and C) Alternatively, internalized virus particles can escape from the endosomal network. This is often dependent on endosome acidification and occurs at either mild pH (6.5-6) from the early endosome (B) or low pH (5.5-4) from late endosome and/or lysosome (C). In addition to the acidic environment, other molecular cues may be required to trigger fusion/penetration, for example, membrane lipid content (Semliki Forest virus and Dengue virus) or proteolytic cleavage (reovirus and SARS coronavirus; Skehel et al., 1982; Schlegel and Wade, 1984; Mothes et al., 2000; Brabec et al., 2003) . (D) Polyomaviruses such as SV40 undergo atypical transport through the endosomal pathway to the ER, where partially disassembled virus particles are shuttled to the cytosol by the retrotranslocation machinery.