A conformational change in Sindbis virus glycoproteins E1 and E2 is detected at the plasma membrane as a consequence of early virus-cell interaction.
A conformational change in the structure of Sindbis (SB) virus was detected after virion attachment to baby hamster kidney cells but before internalization. The alteration was manifested as increased virion binding of certain glycoprotein E1 and E2 monoclonal antibodies (MAbs) that recognized transitional epitopes. These epitopes were inaccessible to MAb on native virions but became accessible to their cognate MAbs in the early stages of infection. Transit of virions through a low-pH compartment apparently was not required for the conformational change. Exposure of transitional epitopes was unaffected by treatment of BHK cells with NH4Cl and occurred normally in Chinese hamster ovary cells temperature sensitive for endosomal acidification. However, the rearrangement was correlated with both the time course and temperature dependence of SB virus penetration, and the rearrangement occurred earlier with an SB virus mutant having an accelerated penetration phenotype. In addition, MAb to a transitional epitope, a probe specific for rearranged particles, retarded penetration of infectious virions. These results suggested that the SB virus E1/E2 glycoprotein spike undergoes a structural rearrangement as a consequence of virion interaction with the cell surface and that this altered virion form may be an important early intermediate in an entry pathway leading to productive infection.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599-7290.
D C
DC
Flynn
W J
WJ
Meyer
J M
JM
Mackenzie
R E
RE
Johnston
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral / Q000032:analysis; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology; D000939:Epitopes / Q000032:analysis; D007074:Immunoglobulin G; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation; D012845:Sindbis Virus / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D014771:Virion / Q000502:physiology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C022012:glycoprotein E1, Sindbis virus; C064950:glycoprotein E2, Sindbis virus; D000643:Ammonium Chloride; D003513:Cycloheximide