In vitro analysis of factors involved in the disassembly of Sindbis virus cores by 60S ribosomal subunits identifies a possible role of low pH.
Disassembly of alphavirus cores early in infection involves interaction of the core with 60S ribosomal subunits. This interaction might be subjected to regulatory processes. We have established an in vitro system of core disassembly in order to identify cellular proteins involved in the regulation of disassembly. No evidence for the existence of such proteins was found, but it became apparent that certain organic solvents and detergents or a high proton concentration (pH 6.0) stimulated core disassembly. Alphaviruses infect cells by an endosomal pathway. The low pH in the endosome activates a fusion activity of the viral surface protein E1 and leads to fusion of the viral membrane with the endosomal membrane, followed by release of the core into the cytoplasm. Since the presence of the E1 protein in the plasma membrane of infected cells leads to increased membrane permeability at low pH, our findings indicate that disassembly of alphavirus cores could be regulated by the proton concentration. We propose that the viral membrane proteins present in the endosomal membrane after fusion form a pore, which allows the flow of protons from the endosome into the cytoplasm. This process would generate a region of low pH in the cytoplasm at the correct time and place to allow the efficient disassembly of the incoming viral core by 60S subunits.
Wengler
Gerd
G
Institut für Virologie der Veterinärmedizin, Justus-Liebig-Universität Giessen, 35392 Giessen, Germany1.
Wengler
Gisela
G
Institut für Virologie der Veterinärmedizin, Justus-Liebig-Universität Giessen, 35392 Giessen, Germany1.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D003902:Detergents; D004121:Dimethyl Sulfoxide; D006863:Hydrogen-Ion Concentration; D017830:Octoxynol; D011092:Polyethylene Glycols; D012270:Ribosomes / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D012845:Sindbis Virus / Q000378:metabolism* / Q000502:physiology; D012997:Solvents; D014758:Viral Core Proteins / Q000378:metabolism*
D003902:Detergents; D012997:Solvents; D014758:Viral Core Proteins; D011092:Polyethylene Glycols; D017830:Octoxynol; C010615:Nonidet P-40; D012697:Serine Endopeptidases; C101665:core protein, Sindbis virus; D004121:Dimethyl Sulfoxide