FORMATION AND REARRANGEMENT OF DISULFIDE BONDS DURING MATURATION OF THE SINDBIS VIRUS E1 GLYCOPROTEIN

The rigidly ordered icosahedral lattice of the Sindbis virus envelope is composed of a host-derived membrane bilayer in which the viral glycoproteins El and E2 reside. E1-E1 interactions stabilized by intramolecular disulfide bridges play a significant role in maintaining the envelope's structural integrity (R. P. Anthony and D. T. Broan, J. Virol. 65:1187-1194, 1991; R. P. Anthony, A. M. Paredes, and D. T. Brown, Virology 190:330-336, 1992). We have examined the acquisition of disulfide bridges within El during its maturation. Prior to exit from the endoplasmic reticulum, El folds via at least three intermediates, differing in the number and/or arrangement of their disulfides, into a single, compact form. This El species remains stable with respect to its disulfides until late in the secretory pathway, when El attains a metastable conformation. At this point, when appropriately triggered, intramolecular thiol-disulfide exchange reactions within El can occur, resulting in the generation of alternative El species. This metastable nature of mature El may have important implications for the mechanism of virus disassembly during the initial stages of the infection process