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PMID: 15367645 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The signal peptide of the Junín arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature G1-G2 complex.

Journal of virology ·Vol. 78 ·No. 19 ·2004-10-00 ·Pages 10783-92

York J, Romanowski V, Lu M, Nunberg JH

Abstract

Arenaviruses comprise a diverse family of rodent-borne viruses that are responsible for recurring and emerging outbreaks of viral hemorrhagic fevers worldwide. The Junín virus, a member of the New World arenaviruses, is endemic to the pampas grasslands of Argentina and is the etiologic agent of Argentine hemorrhagic fever. In this study, we have analyzed the assembly and function of the Junín virus envelope glycoproteins. The mature envelope glycoprotein complex is proteolytically processed from the GP-C precursor polypeptide and consists of three noncovalently associated subunits, G1, G2, and a stable 58-amino-acid signal peptide. This tripartite organization is found both on virions of the attenuated Candid 1 strain and in cells expressing the pathogenic MC2 strain GP-C gene. Replacement of the Junín virus GP-C signal peptide with that of human CD4 has little effect on glycoprotein assembly while abolishing the ability of the G1-G2 complex to mediate pH-dependent cell-cell fusion. In addition, we demonstrate that the Junín virus GP-C signal peptide subunit is myristoylated at its N-terminal glycine. Alanine substitution for the modified glycine residue in the GP-C signal peptide does not affect formation of the tripartite envelope glycoprotein complex but markedly reduces its membrane fusion activity. In contrast to the classical view that signal peptides act primarily in targeting nascent polypeptides to the endoplasmic reticulum, we suggest that the signal peptide of the arenavirus GP-C may serve additional functions in envelope glycoprotein structure and trafficking.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Animals CD4 Antigens/genetics,metabolism Cell Fusion Chlorocebus aethiops Conserved Sequence Glycoproteins/chemistry,metabolism Hydrogen-Ion Concentration Junin virus/chemistry Membrane Fusion Molecular Sequence Data Protein Precursors/chemistry,metabolism Protein Processing, Post-Translational Protein Sorting Signals/physiology Protein Subunits/metabolism Sequence Homology, Amino Acid Vero Cells Viral Envelope Proteins/chemistry,metabolism Viral Fusion Proteins/chemistry,metabolism
Chemicals
CD4 Antigens Glycoproteins Protein Precursors Protein Sorting Signals Protein Subunits Viral Envelope Proteins Viral Fusion Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
York Joanne
Montana Biotechnology Center, The University of Montana, Missoula, MT 59812, USA.
Romanowski Victor
Lu Min
Nunberg Jack H
References (70)
70 references, click to expand
  1. Kinetics and pH dependence of acid-induced structural changes in the lymphocytic choriomeningitis virus glycoprotein complex.
    Virology. 1995 May 10;209(1):3-9 PMID: 7747483
  2. The inhibitory activity of an HIV type 1 peptide correlates with its ability to interact with a leucine zipper structure.
    AIDS Res Hum Retroviruses. 1995 Mar;11(3):323-5 PMID: 7786578
  3. The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.
    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9871-5 PMID: 7568235
  4. Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions.
    J Virol. 1996 Jan;70(1):341-51 PMID: 8523546
  5. PHD: predicting one-dimensional protein structure by profile-based neural networks.
    Methods Enzymol. 1996;266:525-39 PMID: 8743704
  6. Low-pH-induced fusion of Vero cells infected with Junin virus.
    Arch Virol. 1996;141(7):1307-17 PMID: 8774689
  7. Dilation of the influenza hemagglutinin fusion pore revealed by the kinetics of individual cell-cell fusion events.
    J Cell Biol. 1996 Oct;135(1):63-71 PMID: 8858163
  8. Interactions between PE2, E1, and 6K required for assembly of alphaviruses studied with chimeric viruses.
    J Virol. 1996 Nov;70(11):7910-20 PMID: 8892914
  9. Virus-cell and cell-cell fusion.
    Annu Rev Cell Dev Biol. 1996;12:627-61 PMID: 8970739
  10. Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry.
    J Biol Chem. 2002 Dec 27;277(52):50579-88 PMID: 12218051
  11. Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P.
    J Virol. 2003 Mar;77(5):2866-72 PMID: 12584310
  12. Signal peptide of Lassa virus glycoprotein GP-C exhibits an unusual length.
    FEBS Lett. 2003 Mar 13;538(1-3):203-6 PMID: 12633879
  13. Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus.
    Science. 1998 Dec 11;282(5396):2079-81 PMID: 9851928
  14. Human immunodeficiency virus type 1 protease triggers a myristoyl switch that modulates membrane binding of Pr55(gag) and p17MA.
    J Virol. 1999 Mar;73(3):1902-8 PMID: 9971769
  15. Structural basis for membrane fusion by enveloped viruses.
    Mol Membr Biol. 1999 Jan-Mar;16(1):3-9 PMID: 10332732
  16. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.
    Protein Eng. 1997 Jan;10(1):1-6 PMID: 9051728
  17. The glycoprotein precursor gene of the attenuated Junin virus vaccine strain (Candid #1).
    Am J Trop Med Hyg. 1997 Feb;56(2):216-25 PMID: 9080883
  18. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  19. Molecular characterization of attenuated Junin virus strains.
    J Gen Virol. 1997 Jul;78 ( Pt 7):1605-10 PMID: 9225036
  20. Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group.
    J Infect Dis. 1998 Feb;177(2):277-83 PMID: 9466512
  21. Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected].
    J Virol. 2003 Oct;77(19):10700-5 PMID: 12970458
  22. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.
    Nat Med. 1998 Nov;4(11):1302-7 PMID: 9809555
  23. Myristic acid analogs are inhibitors of Junin virus replication.
    Microbes Infect. 1999 Jul;1(8):609-14 PMID: 10611737
  24. A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure.
    J Virol. 2000 Jan;74(2):627-43 PMID: 10623724
  25. Influenza virus assembly and lipid raft microdomains: a role for the cytoplasmic tails of the spike glycoproteins.
    J Virol. 2000 May;74(10):4634-44 PMID: 10775599
  26. A particle-associated glycoprotein signal peptide essential for virus maturation and infectivity.
    J Virol. 2001 Jul;75(13):5762-71 PMID: 11390578
  27. Towards a human Lassa fever vaccine.
    Rev Med Virol. 2001 Sep-Oct;11(5):331-41 PMID: 11590670
  28. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P.
    Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12701-5 PMID: 11606739
  29. Palmitoylation of the Rous sarcoma virus transmembrane glycoprotein is required for protein stability and virus infectivity.
    J Virol. 2001 Dec;75(23):11544-54 PMID: 11689636
  30. Mechanisms of viral membrane fusion and its inhibition.
    Annu Rev Biochem. 2001;70:777-810 PMID: 11395423
  31. N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence.
    J Mol Biol. 2002 Apr 5;317(4):541-57 PMID: 11955008
  32. New World arenavirus clade C, but not clade A and B viruses, utilizes alpha-dystroglycan as its major receptor.
    J Virol. 2002 May;76(10):5140-6 PMID: 11967329
  33. Arenaviruses: genomic RNAs, transcription, and replication.
    Curr Top Microbiol Immunol. 2002;262:139-57 PMID: 11987804
  34. Arenaviruses: protein structure and function.
    Curr Top Microbiol Immunol. 2002;262:159-73 PMID: 11987805
  35. Lipid rafts and assembly of enveloped viruses.
    Traffic. 2002 Oct;3(10):705-9 PMID: 12230468
  36. The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor.
    BMC Microbiol. 2001;1:1 PMID: 11208257
  37. Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins.
    Biochim Biophys Acta. 1999 Aug 12;1451(1):1-16 PMID: 10446384
  38. The PROSITE database, its status in 1999.
    Nucleic Acids Res. 1999 Jan 1;27(1):215-9 PMID: 9847184
  39. Progressive truncations C terminal to the membrane-spanning domain of simian immunodeficiency virus Env reduce fusogenicity and increase concentration dependence of Env for fusion.
    J Virol. 2003 Jun;77(12):7067-77 PMID: 12768026
  40. Virus entry, assembly, budding, and membrane rafts.
    Microbiol Mol Biol Rev. 2003 Jun;67(2):226-37, table of contents PMID: 12794191
  41. Modulation of entry of enveloped viruses by cholesterol and sphingolipids (Review).
    Mol Membr Biol. 2003 Jul-Sep;20(3):243-54 PMID: 12893532
  42. Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions.
    Virology. 2003 Sep 15;314(1):168-78 PMID: 14517070
  43. Long-lived signal peptide of lymphocytic choriomeningitis virus glycoprotein pGP-C.
    J Biol Chem. 2003 Oct 24;278(43):41914-20 PMID: 12917426
  44. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12978-83 PMID: 14563923
  45. Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor.
    EMBO Rep. 2003 Nov;4(11):1084-8 PMID: 14555961
  46. Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion.
    Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14610-7 PMID: 14561897
  47. Lassa virus glycoprotein signal peptide displays a novel topology with an extended endoplasmic reticulum luminal region.
    J Biol Chem. 2004 Mar 26;279(13):12293-9 PMID: 14709548
  48. Role of hydrophobic residues in the central ectodomain of gp41 in maintaining the association between human immunodeficiency virus type 1 envelope glycoprotein subunits gp120 and gp41.
    J Virol. 2004 May;78(9):4921-6 PMID: 15078976
  49. Identification of a virus-specified protein in the nucleus of vaccinia virus-infected cells.
    J Gen Virol. 1980 Apr;47(2):293-9 PMID: 7365469
  50. Importance of dose of neutralising antibodies in treatment of Argentine haemorrhagic fever with immune plasma.
    Lancet. 1984 Aug 4;2(8397):255-6 PMID: 6146809
  51. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain.
    Cell. 1986 Nov 7;47(3):333-48 PMID: 3094962
  52. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase.
    Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 PMID: 3095828
  53. Myristylation of picornavirus capsid protein VP4 and its structural significance.
    Nature. 1987 Jun 11-17;327(6122):482-6 PMID: 3035380
  54. Junin virus monoclonal antibodies: characterization and cross-reactivity with other arenaviruses.
    J Gen Virol. 1989 May;70 ( Pt 5):1125-32 PMID: 2471803
  55. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 PMID: 2788277
  56. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1.
    Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 PMID: 2405382
  57. Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly.
    AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 PMID: 2194551
  58. Protein-protein interactions in lymphocytic choriomeningitis virus.
    Virology. 1991 Aug;183(2):620-9 PMID: 1853564
  59. Deacylation of the hemagglutinin of influenza A/Aichi/2/68 has no effect on membrane fusion properties.
    Virology. 1991 Sep;184(1):445-8 PMID: 1871979
  60. Toward a vaccine against Argentine hemorrhagic fever.
    Bull Pan Am Health Organ. 1991;25(2):118-26 PMID: 1654168
  61. Molecular organization of Junin virus S RNA: complete nucleotide sequence, relationship with other members of the Arenaviridae and unusual secondary structures.
    J Gen Virol. 1991 Sep;72 ( Pt 9):2129-41 PMID: 1654373
  62. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface.
    Cell. 1992 Feb 7;68(3):533-44 PMID: 1531449
  63. Myristylation of poliovirus capsid precursor P1 is required for assembly of subviral particles.
    J Virol. 1992 Jul;66(7):4556-63 PMID: 1318418
  64. Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein cytoplasmic domain blocks virus infectivity.
    J Virol. 1992 Nov;66(11):6616-25 PMID: 1357190
  65. Ribonuclease S-peptide as a carrier in fusion proteins.
    Protein Sci. 1993 Mar;2(3):348-56 PMID: 8453373
  66. Mechanism of lymphocytic choriomeningitis virus entry into cells.
    Virology. 1994 Jan;198(1):1-9 PMID: 8259643
  67. Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters the conformation of the external domain.
    J Virol. 1994 Feb;68(2):585-91 PMID: 8289362
  68. Acidic pH triggers LCMV membrane fusion activity and conformational change in the glycoprotein spike.
    Virology. 1994 Feb;198(2):455-65 PMID: 8291229
  69. The entry of Junin virus into Vero cells.
    Arch Virol. 1994;136(3-4):363-74 PMID: 8031239
  70. Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation.
    J Virol. 1994 Sep;68(9):5411-22 PMID: 8057423
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.78.19.10783-10792.2004
Published
2004-10-00
Pages
10783-92
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC516395
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.78.19.10783-10792.2004 PMC Full Text View journal details
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