title: Requirement of the vesicular system for membrane permeabilization by Sindbis virus.
abstract: The vast majority of animal viruses enhance membrane permeability at two moments of infection. Herein, we describe that the entry of Sindbis virus (SV) in BHK cells promotes the co-entry of the macromolecule alpha-sarcin into the cytoplasm, thereby blocking translation. At a later stage, this protein toxin cannot enter the cell, while low molecular weight compounds, such as hygromycin B, readily pass through the plasma membrane of Sindbis virus-infected BHK cells. To unveil the participation of the different Sindbis virus structural proteins in late permeabilization, transfection experiments with each late gene by separate have been carried out. Our findings indicate that 6K is the main determinant that enhances membrane permeabilization. The co-expression of both viral glycoproteins employing a Sindbis virus variant that lacks the entire 6K gene partly modifies membrane permeability. Brefeldin A, a macrolide antibiotic that interferes with the proper functioning of the vesicular system, hampers the induction of membrane leakiness without significantly affecting viral protein synthesis. On the other hand, the flavone compound Ro-090179 also diminishes the entry of hygromycin B, while bafilomycin A1 or nocodazole have no effect. These data reveal the requirement of the vesicular system for late viral membrane permeabilization.
authors.affiliation: Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. mvmadan@cbm.uam.es
authors.forename: Vanessa
authors.initials: V
authors.lastname: Madan
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Sanz
authors.forename: Luis
authors.initials: L
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D020126:Brefeldin A / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D006224:Cricetinae; D007668:Kidney / Q000166:cytology / Q000821:virology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012845:Sindbis Virus / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D020126:Brefeldin A