The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

Receptor engagement initiates events that enable viruses to transit the barrier imposed by the plasma membrane and associated structures. In most cells, the cortex (an elaborate network of actin fibers, actin-binding proteins, membrane-linker proteins [e.g., ERM proteins], motor proteins, and other components tens of nanometers thick) supports and modulates the physical and dynamic properties of the plasma membrane (Taylor et al., 2011) . From the virus perspective, little attention has been paid to the actin cortex, in part because of the paucity of tools to study the structure but also because of the extent to which the cortex varies in different cell types, particularly in tissue culture lines. The cortex has the potential to prevent or delay the transit of large molecular assemblies from the cytoplasm toward the plasma membrane-for example, it excludes ribosomes from regions adjacent to the plasma membrane-and presumably similarly restricts incoming virus particles (Marsh and Bron, 1997) . In the few examples in which it has been studied, virus-induced receptor-mediated signaling can cause local actin perturbation to allow viruses that undergo penetration at the cell surface to transit the cortex (Fig. 1 B ; Wang et al., 2005; Yoder et al., 2008; Taylor et al., 2011) . For HIV, Env engagement with the coreceptor CXCR4 on resting CD4 +ve T cells leads to G i signaling and subsequent activation of the actin-depolymerizing protein cofilin to induce local cortex reorganization that facilitates infection (Yoder et al., 2008) . Cross-linking EGFR and v3 integrin by human cytomegalovirus at the cell surface results in the cooperative activation of phosphoinositide 3-kinase (PI3K) and Src, culminating in actin reorganization through RhoA and cofilin, events that correlate with translocation of human cytomegalovirus capsids to the nucleus and infection (Wang et al., 2005) .