Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH.
The flavivirus envelope protein E undergoes irreversible conformational changes at a mildly acidic pH which are believed to be necessary for membrane fusion in endosomes. In this study we used a combination of chemical cross-linking and sedimentation analysis to show that the envelope proteins of the flavivirus tick-borne encephalitis virus also change their oligomeric structure when exposed to a mildly acidic environment. Under neutral or slightly alkaline conditions, protein E on the surface of native virions exists as a homodimer which can be isolated by solubilization with the nonionic detergent Triton X-100. Solubilization with the same detergent after pretreatment at an acidic pH, however, yielded homotrimers rather than homodimers, suggesting that exposure to an acidic pH had induced a simultaneous weakening of dimeric contacts and a strengthening of trimeric ones. The pH threshold for the dimer-to-trimer transition was found to be 6.5. Because the pH dependence of this transition parallels that of previously observed changes in the conformation and hydrophobicity of protein E and that of virus-induced membrane fusion, it appears likely that the mechanism of fusion with endosomal membranes involves a specific rearrangement of the proteins in the viral envelope. Immature virions in which protein E is associated with the uncleaved precursor (prM) of the membrane protein M did not undergo a low-pH-induced rearrangement. This is consistent with a protective role of protein prM for protein E during intracellular transport of immature virions through acidic compartments of the trans-Golgi network.
Allison
S L
SL
Institute of Virology, University of Vienna, Austria.
Schalich
J
J
Stiasny
K
K
Mandl
C W
CW
Kunz
C
C
Heinz
F X
FX
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002499:Centrifugation, Density Gradient; D002642:Chick Embryo; D004669:Encephalitis Viruses, Tick-Borne / Q000737:chemistry*; D000939:Epitopes; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D014759:Viral Envelope Proteins