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Journal of Virology, November 2007, p. 12515-12524, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01481-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Signal Peptide Requirements for Lymphocytic Choriomeningitis Virus Glycoprotein C Maturation and Virus Infectivity

Sabrina Schrempf,^1, Marc Froeschke,^1, Tsanan Giroglou,² Dorothee von Laer,² and Bernhard Dobberstein^1*

Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany,¹ Georg Speyer Haus, Institute for Biomedical Research, Frankfurt University Medical School, 60596 Frankfurt, Germany²

Received 6 July 2007/ Accepted 24 August 2007

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.

Published ahead of print on 5 September 2007.

S.S. and M.F. contributed equally to this work.

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