Arenavirus Stable Signal Peptide Is the Keystone Subunit for Glycoprotein Complex Organization

Bederka, Lydia H.; Bonhomme, Cyrille J.; Ling, Emily L.; Buchmeier, Michael J.

Using truncated glycoprotein constructs, previous authors reported that SSP is dispensable for GP ectodomain expression (42) . Our current results contrast previous findings, as we used, or reconstituted, full-length glycoprotein expression vectors and not truncated plasmid constructs. The presence of the signal peptide was required for proper, full-length glycoprotein ectodomain processing (43) . Our results further differed from previous research using both Old World and New World arenavirus glycoproteins in that the LCMV Armstrong strain (Arm-4) glycoprotein does not utilize basic residues within the GP2 cytoplasmic domain as the driving force for ER exit (12, 33) . Our mutational analysis of the GP1/2 subunit containing a mutated basic motif at the ultimate portion of the GP2 cytoplasmic domain did not result in any cleaved GP2 subunit, indicating that this glycoprotein lacking its SSP was not capable of exiting the ER for proteolytic processing. When wild-type SSP was coexpressed with the mutated GP1/2, we detected the processed GP2 subunit. Additionally, our results contrasted Lassa glycoprotein studies which indicated the GP2 cytoplasmic domain played a role in GP maturation cleavage, although the authors did not use a full-length Lassa glycoprotein in their characterizations (44) .