Identification of a novel consensus sequence at the cleavage site of the lassa virus glycoprotein

The Lassa virus glycoprotein consists of an amino-terminal and a carboxy-te rminal cleavage fragment designated GP-1 and GP-2, respectively, that are d erived by proteolysis from the precursor GP-C. The membrane-anchored GP-2 o btained from purified virions of the Josiah strain revealed the N-terminal tripeptide GTF(262) when analyzed by Edman degradation. Upstream of this si te, GP-C contains the tetrapeptide sequence RRLL259, which is conserved in all Lassa virus isolates published to date. Systematic mutational analysis of vector-expressed GP-C revealed that the motif R-X (L/I/V)-L-259 (where X stands for L, I, or V) is essential for cleavage of the peptide bond betwe en leucine(259) and glycine(260). This cleavage motif is homologous to the consensus sequence recognized by a novel class of cellular endoproteases wh ich have so far not been implicated in the processing of viral glycoprotein s.