title: Signal peptide requirements for lymphocytic choriomeningitis virus glycoprotein C maturation and virus infectivity.
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 (SP(GP-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, SP(GP-C) accumulates in cells and virus particles. In the present study, we identified the LCMV SP(GP-C) as being an essential component of the GP complex and show that the different regions of SP(GP-C) are required for distinct steps in GP maturation and virus infectivity. More specifically, we show that one hydrophobic region of SP(GP-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 SP(GP-C), on the other hand, is essential for pseudoviral infection of target cells. Furthermore, we show that unmyristoylated SP(GP-C) exposes its N-terminal region to the exoplasmic side. This SP(GP-C) can promote GP-C maturation but is defective in pseudoviral infection. Myristoylation and topology of SP(GP-C) in the membrane may thus hold the key to an understanding of the role of SP(GP-C) in GP-C complex maturation and LCMV infectivity.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schrempf
authors.forename: Marc
authors.initials: M
authors.lastname: Froeschke
authors.forename: Tsanan
authors.initials: T
authors.lastname: Giroglou
authors.forename: Dorothee
authors.initials: D
authors.lastname: von Laer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dobberstein
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization