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 fusion proteins, they use the same physical principles and topology as other fusion proteins to drive membrane fusion. Exposure of a fusion loop first allows it to insert into the host‑cell membrane. Conserved hydrophobic residues in the fusion loop act as an anchor, which penetrates only partway into the outer bilayer leaflet of the host‑cell membrane. Subsequent folding back of the fusion protein on itself directs the C‑terminal viral transmembrane anchor towards the fusion loop. This fold‑back forces the host‑cell membrane (held by the fusion loop) and the viral membrane (held by the C‑terminal transmembrane anchor) against each other, resulting in membrane fusion. In class II fusion proteins, the fold‑back is triggered by the reduced pH of an endosome, and is accompanied by the assembly of fusion protein monomers into trimers. The fold‑back occurs by domain rearrangement rather than by an extensive refolding of secondary structure, but this domain rearrangement and the assembly of monomers into trimers together bury a large surface area. The energy that is thus released exerts a bending force on the apposed viral and cellular membranes, causing them to bend towards each other and, eventually, to fuse.
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...