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.
Enveloped viruses rely on fusion proteins in their envelope to fuse the viral membrane to the host‑cell membrane. This key step in viral entry delivers the viral genome into the cytoplasm for replication. Although class II fusion proteins are genetically and structurally unrelated to class I...
The entry of herpesviruses into their target cells is complex at many levels. Virus entry proceeds by a succession of interactions between viral envelope glycoproteins and molecules on the cell membrane. The process is divided into distinct steps: attachment to the cell surface, interaction...
The family Paramyxoviridae consists of a group of large, enveloped, negative‑sense, single‑stranded RNA viruses and contains many important human and animal pathogens. Molecular and biochemical characterization over the past decade has revealed an extraordinary breadth of biological...
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...
Mammalian orthoreoviruses (reoviruses) are members of the Reoviridae. Reoviruses contain 10 double‑stranded (ds) RNA gene segments enclosed in two concentric protein shells, called outer capsid and core. These viruses serve as a versatile experimental system for studies of viral replication...
As a major pathogen of human and certain animal species, influenza virus causes wide spread and potentially devastating disease. To initiate infection, the virus first binds to cellular receptors comprising either ‑(2,3) or ‑(2,6) linked sialic acid. Recent advances in our understanding of...
The essential event in picornavirus entry is the delivery of the RNA genome to the cytoplasm of a target cell, where replication occurs. In the past several years progress has been made in understanding the structural changes in the virion important for uncoating and RNA release. In addition,...
A number of advances in recent years have significantly furthered our understanding of filovirus attachment and cellular tropism. For example, several cell‑surface molecules have been identified as attachment factors with the potential to facilitate the in vivo targeting of particular cell...
The retrovirus family contains several important human and animal pathogens, including the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Studies with retroviruses were instrumental to our present understanding of the cellular entry of...
Entry is the first step in the infectious life cycle of a virus. In the case of rhabdoviruses, entry is facilitated exclusively by the envelope glycoprotein G and its interactions with the host cell. For vesicular stomatitis virus (VSV), attachment to the cell surface was thought to be...