title: Role of the stable signal peptide and cytoplasmic domain of G2 in regulating intracellular transport of the Junín virus envelope glycoprotein complex.
abstract: Enveloped viruses utilize the membranous compartments of the host cell for the assembly and budding of new virion particles. In this report, we have investigated the biogenesis and trafficking of the envelope glycoprotein (GP-C) of the Junín arenavirus. The mature GP-C complex is unusual in that it retains a stable signal peptide (SSP) as an essential component in association with the typical receptor-binding (G1) and transmembrane fusion (G2) subunits. We demonstrate that, in the absence of SSP, the G1-G2 precursor is restricted to the endoplasmic reticulum (ER). This constraint is relieved by coexpression of SSP in trans, allowing transit of the assembled GP-C complex through the Golgi and to the cell surface, the site of arenavirus budding. Transport of a chimeric CD4 glycoprotein bearing the transmembrane and cytoplasmic domains of G2 is similarly regulated by SSP association. Truncations to the cytoplasmic domain of G2 abrogate SSP association yet now permit transport of the G1-G2 precursor to the cell surface. Thus, the cytoplasmic domain of G2 is an important determinant for both ER localization and its control through SSP binding. Alanine mutations to either of two dibasic amino acid motifs in the G2 cytoplasmic domain can also mobilize the G1-G2 precursor for transit through the Golgi. Taken together, our results suggest that SSP binding masks endogenous ER localization signals in the cytoplasmic domain of G2 to ensure that only the fully assembled, tripartite GP-C complex is transported for virion assembly. This quality control process points to an important role of SSP in the structure and function of the arenavirus envelope glycoprotein.
authors.affiliation: Montana Biotechnology Center, and Division of Biological Sciences, The University of Montana, Science Complex Room 221, Missoula, MT 59812, USA.
authors.forename: Sudhakar S
authors.initials: SS
authors.lastname: Agnihothram
authors.forename: Joanne
authors.initials: J
authors.lastname: York
authors.forename: Jack H
authors.initials: JH
authors.lastname: Nunberg
mesh_terms: D000818:Animals; D001692:Biological Transport; D002522:Chlorocebus aethiops; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018051:Junin virus / Q000737:chemistry*; D021382:Protein Sorting Signals / Q000502:physiology*; D017434:Protein Structure, Tertiary; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins