title: Cell entry of enveloped viruses.
abstract: Enveloped viruses penetrate their cell targets following the merging of their membrane with that of the cell. This fusion process is catalyzed by one or several viral glycoproteins incorporated on the membrane of the virus. These envelope glycoproteins (EnvGP) evolved in order to combine two features. First, they acquired a domain to bind to a specific cellular protein, named "receptor." Second, they developed, with the help of cellular proteins, a function of finely controlled fusion to optimize the replication and preserve the integrity of the cell, specific to the genus of the virus. Following the activation of the EnvGP either by binding to their receptors and/or sometimes the acid pH of the endosomes, many changes of conformation permit ultimately the action of a specific hydrophobic domain, the fusion peptide, which destabilizes the cell membrane and leads to the opening of the lipidic membrane. The comprehension of these mechanisms is essential to develop medicines of the therapeutic class of entry inhibitor like enfuvirtide (Fuzeon) against human immunodeficiency virus (HIV). In this chapter, we will summarize the different envelope glycoprotein structures that viruses develop to achieve membrane fusion and the entry of the virus. We will describe the different entry pathways and cellular proteins that viruses have subverted to allow infection of the cell and the receptors that are used. Finally, we will illustrate more precisely the recent discoveries that have been made within the field of the entry process, with a focus on the use of pseudoparticles. These pseudoparticles are suitable for high-throughput screenings that help in the development of natural or artificial inhibitors as new therapeutics of the class of entry inhibitors.
authors.affiliation: Université de Lyon, UCB-Lyon1, IFR128, Lyon, France.
authors.forename: François-Loic
authors.initials: FL
authors.lastname: Cosset
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D057166:High-Throughput Screening Assays; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008561:Membrane Fusion; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D011485:Protein Binding; D058849:Protein Refolding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D014777:Virus Diseases / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D014780:Viruses / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D000077560:Enfuvirtide