title: Lipids Cooperate with the Reovirus Membrane Penetration Peptide to Facilitate Particle Uncoating.
abstract: Virus-host interactions play a role in many stages of the viral lifecycle, including entry. Reovirus, a model system for studying the entry mechanisms of nonenveloped viruses, undergoes a series of regulated structural transitions that culminate in delivery of the viral genetic material. Lipids can trigger one of these conformational changes, infectious subviral particle (ISVP)-to-ISVP* conversion. ISVP* formation releases two virally encoded peptides, myristoylated μ1N (myr-μ1N) and Φ. Among these, myr-μ1N is sufficient to form pores within membranes. Released myr-μ1N can also promote ISVP* formation in trans Using thermal inactivation as a readout for ISVP-to-ISVP* conversion, we demonstrate that lipids render ISVPs less thermostable in a virus concentration-dependent manner. Under conditions in which neither lipids alone nor myr-μ1N alone promotes ISVP-to-ISVP* conversion, myr-μ1N induces particle uncoating when lipids are present. These data suggest that the pore-forming activity and the ISVP*-promoting activity of myr-μ1N are linked. Lipid-associated myr-μ1N interacts with ISVPs and triggers efficient ISVP* formation. The cooperativity between a reovirus component and lipids reveals a distinct virus-host interaction in which membranes can facilitate nonenveloped virus entry.
authors.affiliation: From the Department of Biology, Indiana University, Bloomington, Indiana 47405.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Snyder
authors.affiliation: From the Department of Biology, Indiana University, Bloomington, Indiana 47405 pdanthi@indiana.edu.
authors.forename: Pranav
authors.initials: P
authors.lastname: Danthi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000821:virology; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D002478:Cells, Cultured; D008081:Liposomes / Q000737:chemistry; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009227:Myristic Acids / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D012087:Reoviridae / Q000502:physiology*; D012088:Reoviridae Infections / Q000378:metabolism* / Q000821:virology; D017386:Sequence Homology, Amino Acid; D014771:Virion / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D057846:Cell-Penetrating Peptides; D008081:Liposomes; D008563:Membrane Lipids; D009227:Myristic Acids
keywords: conformational change; kinetics; membrane; phospholipid vesicle; reovirus; virus entry