Viral Entry into Host Cells

Jolly CL, Sattentau QJ, Clare L. Jolly, Quentin J. Sattentau

Stefan Pöhlmann PhD, Graham Simmons PhD

As obligate intracellular parasites, viruses must bind to, and enter, permissive host cells in order to gain access to the cellular machinery that is required for their replication. The very large number of mammalian viruses identified to date is reflected in the fact that almost every human and animal cell type is a target for infection by one, or commonly more than one, species of virus. As viruses have adapted to target certain cell types for their propagation, there is exquisite specificity in cellular tropism. This specificity is frequently, but not always, mediated by the first step in the viral replication cycle: attachment of viral surface proteins to receptors expressed on susceptible cells. Viral receptors may be protein, carbohydrate, and/or lipid. Many viruses can use more than one attachment receptor, and indeed may sequentially engage multiple receptors to infect a cell. Thus, it is useful to differentiate between attachment receptors, that simply allow viruses a foothold at the limiting membrane of a cell, and entry receptors that mediate delivery the viral genome into the cytoplasm. For some viruses the attachment factors that promote binding to permissive cells are very well defined, but the sequence of events that triggers viral entry is only now beginning to be understood. For other viruses, despite many efforts, the receptors remain elusive. In this chapter we will confine our review to viruses that infect mammals, with particular focus on human pathogens. We do not intend that this will be an exhaustive overview of viral attachment receptors; instead we will take a number of examples of well-characterized virus-receptor interactions, discuss supporting evidence, and highlight any controversies and uncertainties in the field. We will then conclude with a reflection on general principles of viral attachment, consider some exceptions to these principles, and make some suggestion for future research.