ABSTRACT
Insertion of the lymphocytic choriomeningitis virus (LCMV) precursor glycoprotein C (GP-C) into the membrane of the endoplasmic reticulum is mediated by an unusual signal peptide (SPGP-C). It is comprised of 58 amino acid residues and contains an extended hydrophilic N-terminal region, two hydrophobic regions, and a short C-terminal region. After cleavage by signal peptidase, SPGP-C accumulates in cells and virus particles. In the present study, we identified the LCMV SPGP-C as being an essential component of the GP complex and show that the different regions of SPGP-C are required for distinct steps in GP maturation and virus infectivity. More specifically, we show that one hydrophobic region of SPGP-C is sufficient for the membrane insertion of GP-C, while both hydrophobic regions are required for the processing and cell surface expression of the GPs. The N-terminal region of SPGP-C, on the other hand, is essential for pseudoviral infection of target cells. Furthermore, we show that unmyristoylated SPGP-C exposes its N-terminal region to the exoplasmic side. This SPGP-C can promote GP-C maturation but is defective in pseudoviral infection. Myristoylation and topology of SPGP-C in the membrane may thus hold the key to an understanding of the role of SPGP-C in GP-C complex maturation and LCMV infectivity.
Self-Association of Lymphocytic Choriomeningitis Virus Nucleoprotein Is Mediated by Its N-Terminal Region and Is Not Required for Its Anti-Interferon Function