Home LiteratureArticle Details
PMID: 10775599 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Influenza virus assembly and lipid raft microdomains: a role for the cytoplasmic tails of the spike glycoproteins.

Journal of virology ·Vol. 74 ·No. 10 ·2000-05-00 ·Pages 4634-44

Zhang J, Pekosz A, Lamb RA

Abstract

Influenza viruses encoding hemagglutinin (HA) and neuraminidase (NA) glycoproteins with deletions in one or both cytoplasmic tails (HAt- or NAt-) have a reduced association with detergent-insoluble glycolipids (DIGs). Mutations which eliminated various combinations of the three palmitoylation sites in HA exhibited reduced amounts of DIG-associated HA in virus-infected cells. The influenza virus matrix (M(1)) protein was also found to be associated with DIGs, but this association was decreased in cells infected with HAt- or NAt- virus. Regardless of the amount of DIG-associated protein, the HA and NA glycoproteins were targeted primarily to the apical surface of virus-infected, polarized cells. The uncoupling of DIG association and apical transport was augmented by the observation that the influenza A virus M(2) protein as well as the influenza C virus HA-esterase-fusion glycoprotein were not associated with DIGs but were apically targeted. The reduced DIG association of HAt- and NAt- is an intrinsic property of the glycoproteins, as similar reductions in DIG association were observed when the proteins were expressed from cDNA. Examination of purified virions indicated reduced amounts of DIG-associated lipids in the envelope of HAt- and NAt- viruses. The data indicate that deletion of both the HA and NA cytoplasmic tails results in reduced DIG association and changes in both virus polypeptide and lipid composition.

MeSH Terms
Animals Cell Line Cell Polarity Detergents Glycolipids/metabolism HeLa Cells Hemagglutinin Glycoproteins, Influenza Virus/chemistry,metabolism Humans Influenza A virus/chemistry,growth & development,metabolism Influenzavirus C/metabolism Membrane Glycoproteins/metabolism Membrane Lipids/analysis,metabolism Neuraminidase/chemistry,metabolism Solubility Viral Matrix Proteins/metabolism Virion/metabolism Virus Assembly
Chemicals
Detergents Glycolipids Hemagglutinin Glycoproteins, Influenza Virus M-protein, influenza virus Membrane Glycoproteins Membrane Lipids Viral Matrix Proteins Neuraminidase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhang J
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Pekosz A
Lamb R A
References (67)
67 references, click to expand
  1. Cholesterol is required for surface transport of influenza virus hemagglutinin.
    J Cell Biol. 1998 Mar 23;140(6):1357-67 PMID: 9508769
  2. Carbohydrate-mediated Golgi to cell surface transport and apical targeting of membrane proteins.
    EMBO J. 1998 Apr 1;17(7):1919-29 PMID: 9524115
  3. Membrane compartmentation is required for efficient T cell activation.
    Immunity. 1998 Jun;8(6):723-32 PMID: 9655486
  4. Mutations in the middle of the transmembrane domain reverse the polarity of transport of the influenza virus hemagglutinin in MDCK epithelial cells.
    J Cell Biol. 1998 Jul 13;142(1):51-7 PMID: 9660862
  5. A novel mechanism for the acquisition of virulence by a human influenza A virus.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10224-8 PMID: 9707628
  6. GPI-anchored proteins are organized in submicron domains at the cell surface.
    Nature. 1998 Aug 20;394(6695):798-801 PMID: 9723621
  7. Microdomains of GPI-anchored proteins in living cells revealed by crosslinking.
    Nature. 1998 Aug 20;394(6695):802-5 PMID: 9723622
  8. LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation.
    Immunity. 1998 Aug;9(2):239-46 PMID: 9729044
  9. Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains.
    EMBO J. 1998 Sep 15;17(18):5334-48 PMID: 9736612
  10. Annexin XIIIb associates with lipid microdomains to function in apical delivery.
    J Cell Biol. 1998 Sep 21;142(6):1413-27 PMID: 9744874
  11. MAL, a novel integral membrane protein of human T lymphocytes, associates with glycosylphosphatidylinositol-anchored proteins and Src-like tyrosine kinases.
    Eur J Immunol. 1998 Nov;28(11):3675-84 PMID: 9842910
  12. Engagement of GPI-linked CD48 contributes to TCR signals and cytoskeletal reorganization: a role for lipid rafts in T cell activation.
    Immunity. 1998 Dec;9(6):787-96 PMID: 9881969
  13. Apical sorting of bovine enteropeptidase does not involve detergent-resistant association with sphingolipid-cholesterol rafts.
    J Biol Chem. 1999 Jan 15;274(3):1596-605 PMID: 9880538
  14. Influenza viruses select ordered lipid domains during budding from the plasma membrane.
    J Biol Chem. 1999 Jan 22;274(4):2038-44 PMID: 9890962
  15. Functions of lipid rafts in biological membranes.
    Annu Rev Cell Dev Biol. 1998;14:111-36 PMID: 9891780
  16. Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated.
    J Biol Chem. 1999 Feb 5;274(6):3910-7 PMID: 9920947
  17. The MAL proteolipid is necessary for normal apical transport and accurate sorting of the influenza virus hemagglutinin in Madin-Darby canine kidney cells.
    J Cell Biol. 1999 Apr 5;145(1):141-51 PMID: 10189374
  18. VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6241-8 PMID: 10339572
  19. Cell surface expression of biologically active influenza C virus HEF glycoprotein expressed from cDNA.
    J Virol. 1999 Oct;73(10):8808-12 PMID: 10482635
  20. Caveolin, cholesterol and Ras signalling.
    Nat Cell Biol. 1999 Jun;1(2):E35-7 PMID: 10559891
  21. The cytoplasmic tails of the influenza virus spike glycoproteins are required for normal genome packaging.
    Virology. 2000 Apr 10;269(2):325-34 PMID: 10753711
  22. The fluid mosaic model of the structure of cell membranes.
    Science. 1972 Feb 18;175(4023):720-31 PMID: 4333397
  23. Gangliosides of human myelin: sialosylgalactosylceramide (G7) as a major component.
    J Neurochem. 1973 Oct;21(4):829-39 PMID: 4754859
  24. Studies on the formation of the influenza virus envelope.
    Virology. 1974 Aug;60(2):398-418 PMID: 4844421
  25. Evidence for a ninth influenza viral polypeptide.
    Virology. 1978 Nov;91(1):60-78 PMID: 726267
  26. Insertion of influenza M protein into the viral lipid bilayer and localization of site of insertion.
    J Virol. 1981 Oct;40(1):323-8 PMID: 7288926
  27. Analysis of brain lipids by high performance thin-layer chromatography and densitometry.
    J Lipid Res. 1983 Sep;24(9):1243-50 PMID: 6631248
  28. Intracellular transport of influenza virus hemagglutinin to the apical surface of Madin-Darby canine kidney cells.
    J Cell Biol. 1984 Jan;98(1):308-19 PMID: 6707094
  29. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface.
    Cell. 1985 Mar;40(3):627-33 PMID: 3882238
  30. Surface expression of influenza virus neuraminidase, an amino-terminally anchored viral membrane glycoprotein, in polarized epithelial cells.
    Mol Cell Biol. 1985 Sep;5(9):2181-9 PMID: 3016520
  31. Antigenic variation among human strains of influenza C virus detected with monoclonal antibodies to gp88 glycoprotein.
    Virus Res. 1986 Oct;6(1):27-32 PMID: 3799062
  32. Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions.
    J Virol. 1988 Aug;62(8):2762-72 PMID: 2455818
  33. Differential extractability of influenza virus hemagglutinin during intracellular transport in polarized epithelial cells and nonpolar fibroblasts.
    J Cell Biol. 1989 Mar;108(3):821-32 PMID: 2522097
  34. Mechanism of membrane anchoring affects polarized expression of two proteins in MDCK cells.
    Science. 1989 Sep 29;245(4925):1499-501 PMID: 2571189
  35. A glycophospholipid membrane anchor acts as an apical targeting signal in polarized epithelial cells.
    J Cell Biol. 1989 Nov;109(5):2145-56 PMID: 2478564
  36. Vectorial targeting of an endogenous apical membrane sialoglycoprotein and uvomorulin in MDCK cells.
    J Cell Biol. 1990 May;110(5):1533-9 PMID: 2335561
  37. The hemagglutinating glycoproteins of influenza B and C viruses are acylated with different fatty acids.
    Virology. 1990 Aug;177(2):807-11 PMID: 2371783
  38. Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses.
    Virology. 1991 Jun;182(2):475-85 PMID: 2024485
  39. The M2 protein of influenza A virus is acylated.
    J Gen Virol. 1991 Jun;72 ( Pt 6):1461-5 PMID: 2045796
  40. Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant.
    Cell. 1991 Sep 6;66(5):907-20 PMID: 1909606
  41. Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import.
    Cell. 1991 Oct 4;67(1):117-30 PMID: 1913813
  42. 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
  43. Expression of the influenza A virus M2 protein is restricted to apical surfaces of polarized epithelial cells.
    J Virol. 1992 Sep;66(9):5542-52 PMID: 1501289
  44. Glycosphingolipid-enriched, detergent-insoluble complexes in protein sorting in epithelial cells.
    Biochemistry. 1993 Jun 29;32(25):6365-73 PMID: 8518282
  45. Basolateral protein transport in streptolysin O-permeabilized MDCK cells.
    J Cell Biol. 1994 Jun;125(5):1025-35 PMID: 8195286
  46. The influenza virus hemagglutinin cytoplasmic tail is not essential for virus assembly or infectivity.
    EMBO J. 1994 Nov 15;13(22):5504-15 PMID: 7957116
  47. Hyperphosphorylation of mutant influenza virus matrix protein, M1, causes its retention in the nucleus.
    J Virol. 1995 Jan;69(1):439-45 PMID: 7983740
  48. Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior.
    Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12130-4 PMID: 7991596
  49. Analysis of the posttranslational modifications of the influenza virus M2 protein.
    J Virol. 1995 Feb;69(2):1219-25 PMID: 7529332
  50. Involvement of detergent-insoluble complexes in the intracellular transport of intestinal brush border enzymes.
    Biochemistry. 1995 Feb 7;34(5):1596-605 PMID: 7849019
  51. Annexin XIIIb: a novel epithelial specific annexin is implicated in vesicular traffic to the apical plasma membrane.
    J Cell Biol. 1995 Mar;128(6):1043-53 PMID: 7896870
  52. N-glycans as apical sorting signals in epithelial cells.
    Nature. 1995 Nov 2;378(6552):96-8 PMID: 7477300
  53. The cytoplasmic tail of the neuraminidase protein of influenza A virus does not play an important role in the packaging of this protein into viral envelopes.
    Virus Res. 1995 Jun;37(1):37-47 PMID: 7483820
  54. The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication.
    J Virol. 1996 Feb;70(2):873-9 PMID: 8551626
  55. Palmitylation of the influenza virus hemagglutinin (H3) is not essential for virus assembly or infectivity.
    J Virol. 1996 Mar;70(3):1406-14 PMID: 8627657
  56. Membrane association of influenza virus matrix protein does not require specific hydrophobic domains or the viral glycoproteins.
    Virology. 1996 Jun 1;220(1):37-45 PMID: 8659126
  57. Transmembrane domain of influenza virus neuraminidase, a type II protein, possesses an apical sorting signal in polarized MDCK cells.
    J Virol. 1996 Sep;70(9):6508-15 PMID: 8709291
  58. Influenza virus hemagglutinin and neuraminidase glycoproteins stimulate the membrane association of the matrix protein.
    J Virol. 1996 Oct;70(10):6653-7 PMID: 8794300
  59. Characterization of the membrane association of the influenza virus matrix protein in living cells.
    Virology. 1996 Nov 15;225(2):255-66 PMID: 8918911
  60. Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus-infected cells.
    J Virol. 1997 Apr;71(4):2947-58 PMID: 9060654
  61. Influenza virus hemagglutinin and neuraminidase cytoplasmic tails control particle shape.
    EMBO J. 1997 Mar 17;16(6):1236-47 PMID: 9135140
  62. Functional rafts in cell membranes.
    Nature. 1997 Jun 5;387(6633):569-72 PMID: 9177342
  63. High-efficiency incorporation of functional influenza virus glycoproteins into recombinant vesicular stomatitis viruses.
    J Virol. 1997 Aug;71(8):5982-9 PMID: 9223488
  64. Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain.
    EMBO J. 1997 Sep 15;16(18):5501-8 PMID: 9312009
  65. The CM2 protein of influenza C virus is an oligomeric integral membrane glycoprotein structurally analogous to influenza A virus M2 and influenza B virus NB proteins.
    Virology. 1997 Oct 27;237(2):439-51 PMID: 9356355
  66. The O-glycosylated stalk domain is required for apical sorting of neurotrophin receptors in polarized MDCK cells.
    J Cell Biol. 1997 Nov 17;139(4):929-40 PMID: 9362511
  67. The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins.
    EMBO J. 1998 Jan 2;17(1):288-96 PMID: 9427762
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.74.10.4634-4644.2000
Published
2000-05-00
Pages
4634-44
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC111983
Subset
IM
Grants
NIAID NIH HHS · R37 AI020201 · United States
NIAID NIH HHS · R37 AI-20201 · United States
External Links
PubMed source DOI: 10.1128/jvi.74.10.4634-4644.2000 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