Modification of late membrane permeability in avian reovirus-infected cells: viroporin activity of the S1-encoded nonstructural p10 protein.
Infection of chicken embryo fibroblasts by avian reovirus induces an increase in the permeability of the host plasma membrane at late, but not early, infection times. The absence of permeability changes at early infection times, as well as the dependence of late membrane modification on both viral protein synthesis and an active exocytic route, suggest that a virus-encoded membrane protein is required for avian reovirus to permeabilize cells. Further studies revealed that expression of nonstructural p10 protein in bacterial cells arrested cell growth and enhanced membrane permeability. Membrane leakiness was also observed following transient expression of p10 in BSC-40 monkey cells. Both its permeabilizing effect and the fact that p10 shares several structural and physical characteristics with other membrane-active viral proteins indicate that p10 is an avian reovirus viroporin. Furthermore, the fusogenic extracellular NH(2)-terminal domain of p10 appears to be dispensable for permeabilizing activity, because its deletion entirely abolished the fusogenic activity of p10, without affecting its ability to associate with cell membranes and to enhance membrane permeability. Similar properties have reported previously for immunodeficiency virus type I transmembrane glycoprotein gp41. Thus, like gp41, p10 appears to be a multifunctional protein that plays key roles in virus-host interaction.
Bodelón
Gustavo
G
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Labrada
Lucía
L
Martínez-Costas
José
J
Benavente
Javier
J
D000595:Amino Acid Sequence; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002642:Chick Embryo; D004591:Electrophoresis, Polyacrylamide Gel; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism; D000882:Haplorhini; D019476:Insect Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008969:Molecular Sequence Data; D030101:Orthoreovirus, Avian; D012088:Reoviridae Infections / Q000378:metabolism*; D012254:Ribavirin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000378:metabolism
D015700:HIV Envelope Protein gp41; D019476:Insect Proteins; C115616:P10 protein, Periplaneta americana; D014760:Viral Fusion Proteins; D020126:Brefeldin A; D012254:Ribavirin