The cell biology of receptor-mediated virus entry

Grove, Joe; Marsh, Mark

Initial encounters between a virus and a host cell are mediated through viral surface components, either membrane glycoproteins or sites on a viral capsid (Marsh and Helenius, 2006) , binding to glycolipid and/or glycoprotein attachment factors, such as heparan sulfate proteoglycans, on the target cell surface (de Haan et al., 2005; Vlasak et al., 2005) . These first interactions, which may lack specificity, are often electrostatic and serve primarily to give a virus an initial catch-hold from which it can then recruit specific receptors that drive the reactions leading to entry. The receptors are cell surface molecules that provide functions essential for productive infection. In simple situations, receptors can efficiently target viruses for endocytosis ( Fig. 1 A) ; alternatively, receptors may be used to activate specific signaling pathways that facilitate entry, or they may directly drive fusion/penetration events at the surface of a target cell or within endocytic compartments by inducing conformational changes in key virus surface structures (Fig. 1) . In other cases, the reasons underlying the use of specific receptors are more obscure, and a full appreciation will probably require better understanding of the mode of entry of the virus into the hosts, the architecture of target cells within different tissue environments, and the biology of the virus within its hosts. The use of specific cell surface components with restricted expression patterns is frequently responsible for viral tropism, i.e., the ability of a virus to infect a limited set of target cells.