Membrane fusion process of Semliki Forest virus. I: Low pH-induced rearrangement in spike protein quaternary structure precedes virus penetration into cells.
The Semliki Forest virus (SFV) directs the synthesis of a heterodimeric membrane protein complex which is used for virus membrane assembly during budding at the surface of the infected cell, as well as for low pH-induced membrane fusion in the endosomes when particles enter new host cells. Existing evidence suggests that the E1 protein subunit carries the fusion potential of the heterodimer, whereas the E2 subunit, or its intracellular precursor p62, is required for binding to the nucleocapsid. We show here that during virus uptake into acidic endosomes the original E2E1 heterodimer is destabilized and the E1 proteins form new oligomers, presumably homooligomers, with altered E1 structure. This altered structure of E1 is specifically recognized by a monoclonal antibody which can also inhibit penetration of SFV into host cells as well as SFV-mediated cell-cell fusion, thus suggesting that the altered E1 structure is important for the membrane fusion. These results give further support for a membrane protein oligomerization-mediated control mechanism for the membrane fusion potential in alphaviruses.
Department of Molecular Biology, Karolinska Institute, Huddinge, Sweden.
J M
JM
Wahlberg
H
H
Garoff
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D004705:Endocytosis; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008561:Membrane Fusion; D008985:Monensin / Q000494:pharmacology; D011487:Protein Conformation; D012672:Semliki forest virus / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D014357:Trypsin / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D014760:Viral Fusion Proteins / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D046911:Macromolecular Substances; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D008985:Monensin; D014357:Trypsin