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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Salminen, A. Lobigs, M. Liljeström, P. Wahlberg, J. M. Garoff, H. |
| Description | Author Affiliation: Salminen A ( Department of Molecular Biology, Karolinska Institute, Huddinge, Sweden.) |
| Abstract | The envelope of the Semliki Forest virus (SFV) contains two transmembrane proteins, E2 and E1, in a heterodimeric complex. The E2 subunit is initially synthesized as a precursor protein p62, which is proteolytically processed to the mature E2 form before virus budding at the plasma membrane. The p62 (E2) protein mediates binding of the heterodimer to the nucleocapsid during virus budding, whereas E1 carries the entry functions of the virus, that is, cell binding and low pH-mediated membrane fusion activity. We have investigated the significance of the cleavage event for the maturation and entry of the virus. To express SFV with an uncleaved p62 phenotype, BHK-21 cells were transfected by electroporation with infectious viral RNA transcribed from a full-length SFV cDNA clone in which the p62 cleavage site had been changed. The uncleaved p62E1 heterodimer was found to be used for the formation of virus particles with an efficiency comparable to the wild type E2E1 form. However, in contrast to the wild type virus, the mutant virus was virtually noninfectious. Noninfectivity resulted from impaired uptake into cells, as well as from the inability of the virus to promote membrane fusion in the mildly acidic conditions of the endosome. This inability could be reversed by mild trypsin treatment, which converted the viral p62E1 form into the mature E2E1 form, or by treating the virus with a pH 4.5 wash, which in contrast to the more mild pH conditions of endosomes, effectively disrupted the p62E1 subunit association. We conclude that the p62 cleavage is not needed for virus budding, but regulates entry functions of the E1 subunit by controlling the heterodimer stability in acidic conditions. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 2 |
| Volume Number | 116 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1992-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Membrane Fusion Semliki Forest Virus Physiology Viral Envelope Proteins Viral Fusion Proteins Animals Cell Line Chloroquine Pharmacology Cricetinae DNA Mutational Analysis Endocytosis Fluorescent Antibody Technique Hydrogen-Ion Concentration In Vitro Techniques Macromolecular Substances Protein Conformation Trypsin Ultrastructure Virus Replication Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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