Home LiteratureArticle Details
PMID: 16698999 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Role of the stable signal peptide and cytoplasmic domain of G2 in regulating intracellular transport of the Junín virus envelope glycoprotein complex.

Journal of virology ·Vol. 80 ·No. 11 ·2006-06-00 ·Pages 5189-98

Agnihothram SS, York J, Nunberg JH

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.

MeSH Terms
Animals Biological Transport Chlorocebus aethiops Glycoproteins/genetics,metabolism Junin virus/chemistry Protein Sorting Signals/physiology Protein Structure, Tertiary Vero Cells Viral Envelope Proteins/metabolism Viral Fusion Proteins/chemistry,metabolism
Chemicals
Glycoproteins Protein Sorting Signals Viral Envelope Proteins Viral Fusion Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Agnihothram Sudhakar S
Montana Biotechnology Center, and Division of Biological Sciences, The University of Montana, Science Complex Room 221, Missoula, MT 59812, USA.
York Joanne
Nunberg Jack H
References (64)
64 references, click to expand
  1. Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen.
    Science. 1987 Dec 18;238(4834):1704-7 PMID: 3500514
  2. Localization of Bunyamwera bunyavirus G1 glycoprotein to the Golgi requires association with G2 but not with NSm.
    J Gen Virol. 1994 Dec;75 ( Pt 12):3441-51 PMID: 7996137
  3. 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
  4. Long-lived signal peptide of lymphocytic choriomeningitis virus glycoprotein pGP-C.
    J Biol Chem. 2003 Oct 24;278(43):41914-20 PMID: 12917426
  5. Lymphocytic choriomeningitis virus infection in organ transplant recipients--Massachusetts, Rhode Island, 2005.
    MMWR Morb Mortal Wkly Rep. 2005 Jun 3;54(21):537-9 PMID: 15931158
  6. Structural basis for membrane fusion by enveloped viruses.
    Mol Membr Biol. 1999 Jan-Mar;16(1):3-9 PMID: 10332732
  7. The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor.
    BMC Microbiol. 2001;1:1 PMID: 11208257
  8. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood.
    Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11041-8 PMID: 10500120
  9. Analysis of endoplasmic reticulum trafficking signals by combinatorial screening in mammalian cells.
    Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2431-6 PMID: 11226256
  10. 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
  11. Signal peptide of Lassa virus glycoprotein GP-C exhibits an unusual length.
    FEBS Lett. 2003 Mar 13;538(1-3):203-6 PMID: 12633879
  12. 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
  13. Mapping the Golgi targeting and retention signal of Bunyamwera virus glycoproteins.
    J Virol. 2004 Oct;78(19):10793-802 PMID: 15367646
  14. The MHC class II beta chain cytoplasmic tail overcomes the invariant chain p35-encoded endoplasmic reticulum retention signal.
    Int Immunol. 2003 Oct;15(10):1249-63 PMID: 13679394
  15. The entry of Junin virus into Vero cells.
    Arch Virol. 1994;136(3-4):363-74 PMID: 8031239
  16. A trafficking checkpoint controls GABA(B) receptor heterodimerization.
    Neuron. 2000 Jul;27(1):97-106 PMID: 10939334
  17. 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
  18. Biosynthesis and cellular trafficking of the convertase SKI-1/S1P: ectodomain shedding requires SKI-1 activity.
    J Biol Chem. 2002 Mar 29;277(13):11265-75 PMID: 11756446
  19. Mammalian reservoirs of arenaviruses.
    Curr Top Microbiol Immunol. 2002;262:25-63 PMID: 11987807
  20. 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
  21. 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
  22. The Hera database and its use in the characterization of endoplasmic reticulum proteins.
    Bioinformatics. 2004 Apr 12;20(6):937-44 PMID: 14751973
  23. Hide and run. Arginine-based endoplasmic-reticulum-sorting motifs in the assembly of heteromultimeric membrane proteins.
    EMBO Rep. 2005 Aug;6(8):717-22 PMID: 16065065
  24. The signal peptide of the Junín arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature G1-G2 complex.
    J Virol. 2004 Oct;78(19):10783-92 PMID: 15367645
  25. Junin virus monoclonal antibodies: characterization and cross-reactivity with other arenaviruses.
    J Gen Virol. 1989 May;70 ( Pt 5):1125-32 PMID: 2471803
  26. 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
  27. A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.
    Neuron. 1999 Mar;22(3):537-48 PMID: 10197533
  28. 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
  29. Mechanism of lymphocytic choriomeningitis virus entry into cells.
    Virology. 1994 Jan;198(1):1-9 PMID: 8259643
  30. Lassa fever.
    Curr Top Microbiol Immunol. 2002;262:75-109 PMID: 11987809
  31. Construction of a recombinant bacterial human CD4 expression system producing a bioactive CD4 molecule.
    Viral Immunol. 1992 Summer;5(2):163-72 PMID: 1319711
  32. Intracellular localization of Crimean-Congo Hemorrhagic Fever (CCHF) virus glycoproteins.
    Virol J. 2005 Apr 25;2:42 PMID: 15850490
  33. 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
  34. Signal-mediated sorting of membrane proteins between the endoplasmic reticulum and the golgi apparatus.
    Annu Rev Cell Dev Biol. 1996;12:27-54 PMID: 8970721
  35. Acidic pH triggers LCMV membrane fusion activity and conformational change in the glycoprotein spike.
    Virology. 1994 Feb;198(2):455-65 PMID: 8291229
  36. Enveloped viruses: a common mode of membrane fusion?.
    Curr Biol. 1997 Sep 1;7(9):R565-9 PMID: 9285698
  37. Characterization of the Golgi retention motif of Rift Valley fever virus G(N) glycoprotein.
    J Virol. 2002 Dec;76(23):12200-10 PMID: 12414959
  38. Membrane receptor trafficking: evidence of proximal and distal zones conferred by two independent endoplasmic reticulum localization signals.
    Proc Natl Acad Sci U S A. 2003 May 13;100(10):5783-8 PMID: 12724521
  39. Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions.
    Virology. 2003 Sep 15;314(1):168-78 PMID: 14517070
  40. 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
  41. Myristoylation of the RING finger Z protein is essential for arenavirus budding.
    J Virol. 2004 Oct;78(20):11443-8 PMID: 15452271
  42. Human infection with arenaviruses in the Americas.
    Curr Top Microbiol Immunol. 2002;262:65-74 PMID: 11987808
  43. Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junín arenavirus envelope glycoprotein.
    Virology. 2005 Dec 20;343(2):267-74 PMID: 16169032
  44. Bi-directional protein transport between the ER and Golgi.
    Annu Rev Cell Dev Biol. 2004;20:87-123 PMID: 15473836
  45. Steric masking of a dilysine endoplasmic reticulum retention motif during assembly of the human high affinity receptor for immunoglobulin E.
    J Cell Biol. 1995 May;129(4):971-8 PMID: 7744968
  46. Arenaviruses: protein structure and function.
    Curr Top Microbiol Immunol. 2002;262:159-73 PMID: 11987805
  47. Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi.
    Cell. 1999 Dec 23;99(7):703-12 PMID: 10619424
  48. A prospective study of the epidemiology and ecology of Lassa fever.
    J Infect Dis. 1987 Mar;155(3):437-44 PMID: 3805771
  49. An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor.
    J Exp Med. 2005 Feb 21;201(4):555-66 PMID: 15728236
  50. 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
  51. Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor.
    EMBO Rep. 2003 Nov;4(11):1084-8 PMID: 14555961
  52. Identification of a novel consensus sequence at the cleavage site of the Lassa virus glycoprotein.
    J Virol. 2000 Dec;74(23):11418-21 PMID: 11070044
  53. Ribonuclease S-peptide as a carrier in fusion proteins.
    Protein Sci. 1993 Mar;2(3):348-56 PMID: 8453373
  54. Costimulatory properties of the human CD4 molecule: enhancement of CD3-induced T cell activation by human immunodeficiency virus type 1 through viral envelope glycoprotein gp120.
    AIDS Res Hum Retroviruses. 1993 Oct;9(10):945-55 PMID: 7506554
  55. The rubella virus E1 glycoprotein is arrested in a novel post-ER, pre-Golgi compartment.
    J Cell Biol. 1992 Aug;118(4):795-811 PMID: 1500424
  56. Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P.
    J Virol. 2003 Mar;77(5):2866-72 PMID: 12584310
  57. The RXR-type endoplasmic reticulum-retention/retrieval signal of GABAB1 requires distant spacing from the membrane to function.
    Mol Pharmacol. 2005 Jul;68(1):137-44 PMID: 15805225
  58. Mechanisms of viral membrane fusion and its inhibition.
    Annu Rev Biochem. 2001;70:777-810 PMID: 11395423
  59. Folding and assembly of viral membrane proteins.
    Virology. 1993 Apr;193(2):545-62 PMID: 8460475
  60. 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
  61. 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
  62. A soluble form of CD4 (T4) protein inhibits AIDS virus infection.
    Nature. 1988 Jan 7;331(6151):82-4 PMID: 3257544
  63. Giantin, a novel conserved Golgi membrane protein containing a cytoplasmic domain of at least 350 kDa.
    Mol Biol Cell. 1993 Jul;4(7):679-93 PMID: 7691276
  64. Quality control in the endoplasmic reticulum.
    Nat Rev Mol Cell Biol. 2003 Mar;4(3):181-91 PMID: 12612637
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.00208-06
Published
2006-06-00
Pages
5189-98
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1472124
Subset
IM
Grants
NIAID NIH HHS · AI 059355 · United States
NIAID NIH HHS · R21 AI059355 · United States
NCRR NIH HHS · RR 15583 · United States
NCRR NIH HHS · RR 01760 · United States
NCRR NIH HHS · P20 RR015583 · United States
External Links
PubMed source DOI: 10.1128/JVI.00208-06 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2