Home LiteratureArticle Details
PMID: 8253832 Published · ppublish English Journal Article

Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation.

The Journal of cell biology ·Vol. 123 ·No. 6 Pt 1 ·1993-12-00 ·Pages 1309-20

Ruhl M, Himmelspach M, Bahr GM, Hammerschmid F, Jaksche H, Wolff B, Aschauer H, Farrington GK, Probst H, Bevec D

Abstract

Expression of human immunodeficiency virus type 1 (HIV-1) structural proteins requires the presence of the viral trans-activator protein Rev. Rev is localized in the nucleus and binds specifically to the Rev response element (RRE) sequence in viral RNA. Furthermore, the interaction of the Rev activation domain with a cellular cofactor is essential for Rev function in vivo. Using cross-linking experiments and Biospecific Interaction Analysis (BIA) we identify eukaryotic initiation factor 5A (eIF-5A) as a cellular factor binding specifically to the HIV-1 Rev activation domain. Indirect immunofluorescence studies demonstrate that a significant fraction of eIF-5A localizes to the nucleus. We also provide evidence that Rev transactivation is functionally mediated by eIF-5A in Xenopus oocytes. Furthermore, we are able to block Rev function in mammalian cells by antisense inhibition of eIF-5A gene expression. Thus, regulation of HIV-1 gene expression by Rev involves the targeting of RRE-containing RNA to components of the cellular translation initiation complex.

MeSH Terms
Amino Acid Sequence Base Sequence Cell Nucleus/metabolism DNA Primers/chemistry Gene Expression Regulation, Viral Genes, rev HIV-1/genetics HeLa Cells Humans In Vitro Techniques Molecular Sequence Data Nuclear Proteins/metabolism Peptide Initiation Factors/metabolism Peptides/chemistry,metabolism Protein Binding RNA-Binding Proteins Transcriptional Activation
Chemicals
DNA Primers Nuclear Proteins Peptide Initiation Factors Peptides RNA-Binding Proteins eukaryotic translation initiation factor 5A
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Ruhl M
SANDOZ Research Institute, Vienna, Austria.
Himmelspach M
Bahr G M
Hammerschmid F
Jaksche H
Wolff B
Aschauer H
Farrington G K
Probst H
Bevec D
References (75)
75 references, click to expand
  1. Marked enhancement in vivo of adjuvant activity of muramyl dipeptide to protein antigens and to synthetic weak immunogens with monoclonal anti-muramyl dipeptide antibodies.
    Infect Immun. 1985 Aug;49(2):312-9 PMID: 4018873
  2. A second post-transcriptional trans-activator gene required for HTLV-III replication.
    Nature. 1986 May 22-28;321(6068):412-7 PMID: 3012355
  3. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA.
    Cell. 1986 Sep 12;46(6):807-17 PMID: 3638988
  4. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism.
    Cell. 1986 Sep 26;46(7):973-82 PMID: 3530501
  5. Eukaryotic initiation factor 4D. Purification from human red blood cells and the sequence of amino acids around its single hypusine residue.
    J Biol Chem. 1986 Nov 5;261(31):14515-9 PMID: 3095320
  6. A monoclonal antibody against a family of nuclear pore proteins (nucleoporins): O-linked N-acetylglucosamine is part of the immunodeterminant.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6462-6 PMID: 2442757
  7. Use of eukaryotic expression technology in the functional analysis of cloned genes.
    Methods Enzymol. 1987;152:684-704 PMID: 3657593
  8. The art gene product of human immunodeficiency virus is required for replication.
    J Virol. 1988 Feb;62(2):655-8 PMID: 3257271
  9. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1.
    Science. 1988 Feb 19;239(4842):910-3 PMID: 3277284
  10. Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071-5 PMID: 2832844
  11. Subcellular localization of the human immunodeficiency virus trans-acting art gene product.
    J Virol. 1988 Jul;62(7):2498-501 PMID: 2836628
  12. Comparison of the activities of variant forms of eIF-4D. The requirement for hypusine or deoxyhypusine.
    J Biol Chem. 1991 May 5;266(13):7988-94 PMID: 1850732
  13. Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs.
    Genes Dev. 1991 May;5(5):808-19 PMID: 1827422
  14. Characterization of HIV-1 REV protein: binding stoichiometry and minimal RNA substrate.
    Nucleic Acids Res. 1991 Apr 11;19(7):1577-83 PMID: 2027765
  15. Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 1991 Jun;11(6):3105-14 PMID: 1903841
  16. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain.
    J Virol. 1991 Aug;65(8):4248-54 PMID: 2072452
  17. Human immunodeficiency virus type 1 regulator of virion expression, rev, forms nucleoprotein filaments after binding to a purine-rich "bubble" located within the rev-responsive region of viral mRNAs.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7366-70 PMID: 1871141
  18. Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein: a dual function for an arginine-rich binding motif.
    Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7734-8 PMID: 1715576
  19. Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression.
    J Virol. 1991 Oct;65(10):5305-13 PMID: 1895385
  20. Specific regulation of mRNA splicing in vitro by a peptide from HIV-1 Rev.
    Cell. 1991 Oct 4;67(1):169-78 PMID: 1913815
  21. Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation.
    J Virol. 1991 Nov;65(11):5732-43 PMID: 1656066
  22. Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex are functionally interchangeable and share an essential peptide motif.
    J Virol. 1991 Nov;65(11):6001-7 PMID: 1920623
  23. HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA.
    Cell. 1991 Nov 1;67(3):529-36 PMID: 1934059
  24. Functional mapping of the human immunodeficiency virus type 1 Rev RNA binding domain: new insights into the domain structure of Rev and Rex.
    J Virol. 1991 Dec;65(12):7051-5 PMID: 1942257
  25. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein.
    J Virol. 1992 Jan;66(1):150-9 PMID: 1727477
  26. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev protein.
    Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):758-62 PMID: 1731351
  27. Cap recap: the involvement of eIF-4F in regulating gene expression.
    Cell. 1992 Jan 24;68(2):177-180 PMID: 1733496
  28. Differential expression of genes encoding the hypusine-containing translation initiation factor, eIF-5A, in tobacco.
    Nucleic Acids Res. 1992 Feb 25;20(4):665-9 PMID: 1542563
  29. The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs.
    Mol Cell Biol. 1992 Mar;12(3):1375-86 PMID: 1545819
  30. Specific binding of a basic peptide from HIV-1 Rev.
    EMBO J. 1992 Mar;11(3):1119-29 PMID: 1547776
  31. Definition of the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex protein activation domain by functional exchange.
    J Virol. 1992 Apr;66(4):2583-7 PMID: 1548784
  32. Two isoforms of eIF-5A in chick embryo. Isolation, activity, and comparison of sequences of the hypusine-containing proteins.
    J Biol Chem. 1992 Mar 25;267(9):6107-13 PMID: 1556119
  33. The HIV-1 Rev protein: a model system for coupled RNA transport and translation.
    New Biol. 1991 Dec;3(12):1220-32 PMID: 1725960
  34. A fraction of the mRNA 5' cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9612-6 PMID: 1384058
  35. Hypusine: its post-translational formation in eukaryotic initiation factor 5A and its potential role in cellular regulation.
    Biofactors. 1993 May;4(2):95-104 PMID: 8347280
  36. Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes.
    Nature. 1988 Sep 8;335(6186):181-3 PMID: 3412474
  37. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
    Gene. 1988 Jul 15;67(1):31-40 PMID: 3047011
  38. How eukaryotic transcriptional activators work.
    Nature. 1988 Oct 20;335(6192):683-9 PMID: 3050531
  39. Phosphorylation of the rev gene product of human immunodeficiency virus type 1.
    J Virol. 1988 Dec;62(12):4801-4 PMID: 2846891
  40. Functional organization of the nuclear envelope.
    Annu Rev Cell Biol. 1988;4:335-74 PMID: 2461721
  41. Sequence determination and cDNA cloning of eukaryotic initiation factor 4D, the hypusine-containing protein.
    J Biol Chem. 1989 Jan 25;264(3):1578-83 PMID: 2492279
  42. Major nucleolar proteins shuttle between nucleus and cytoplasm.
    Cell. 1989 Feb 10;56(3):379-90 PMID: 2914325
  43. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region.
    J Virol. 1989 Mar;63(3):1265-74 PMID: 2783738
  44. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA.
    Nature. 1989 Mar 16;338(6212):254-7 PMID: 2784194
  45. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 PMID: 2784208
  46. Regulation of human immunodeficiency virus env expression by the rev gene product.
    J Virol. 1989 May;63(5):1959-66 PMID: 2704072
  47. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization.
    Cell. 1989 Jun 30;57(7):1155-65 PMID: 2736624
  48. The human immunodeficiency virus rev protein is a nuclear phosphoprotein.
    Virology. 1989 Jul;171(1):264-6 PMID: 2741343
  49. Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.
    Cell. 1989 Jul 14;58(1):205-14 PMID: 2752419
  50. Identification of four nuclear transport signal-binding proteins that interact with diverse transport signals.
    Mol Cell Biol. 1989 Jul;9(7):3028-36 PMID: 2550792
  51. Protein synthesis initiation factor eIF-4D. Functional comparison of native and unhypusinated forms of the protein.
    J Biol Chem. 1989 Nov 5;264(31):18527-30 PMID: 2509460
  52. The essential role of hypusine in eukaryotic translation initiation factor 4D (eIF-4D). Purification of eIF-4D and its precursors and comparison of their activities.
    J Biol Chem. 1989 Nov 5;264(31):18531-5 PMID: 2509461
  53. Regulation by HIV Rev depends upon recognition of splice sites.
    Cell. 1989 Dec 1;59(5):789-95 PMID: 2686839
  54. Sequence-specific RNA binding by the HIV-1 Rev protein.
    Nature. 1989 Dec 7;342(6250):714-6 PMID: 2556643
  55. Specific binding of HIV-1 recombinant Rev protein to the Rev-responsive element in vitro.
    Nature. 1989 Dec 14;342(6251):816-9 PMID: 2481237
  56. Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function.
    J Virol. 1990 Feb;64(2):881-5 PMID: 2404140
  57. Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA.
    Proc Natl Acad Sci U S A. 1990 Feb;87(3):1198-202 PMID: 2405396
  58. HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence.
    Cell. 1990 Feb 23;60(4):675-83 PMID: 2406030
  59. HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element region.
    Cell. 1990 Feb 23;60(4):685-93 PMID: 1689218
  60. Secondary structure is the major determinant for interaction of HIV rev protein with RNA.
    Science. 1990 Feb 16;247(4944):845-8 PMID: 2406903
  61. Identification of trans-dominant HIV-1 rev protein mutants by direct transfer of bacterially produced proteins into human cells.
    Nucleic Acids Res. 1990 Apr 25;18(8):2037-44 PMID: 2186373
  62. Trans-activating rev protein of the human immunodeficiency virus 1 interacts directly and specifically with its target RNA.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4571-5 PMID: 2191294
  63. Organization of the AKR Qa region: structure of a divergent class I sequence, Q5k.
    J Immunogenet. 1989 Aug-Oct;16(4-5):283-90 PMID: 2639903
  64. Mutants in a conserved region near the carboxy-terminus of HIV-1 Rev identify functionally important residues and exhibit a dominant negative phenotype.
    Virology. 1990 Sep;178(1):327-30 PMID: 2202148
  65. The role of mammalian initiation factor eIF-4D and its hypusine modification in translation.
    Biochim Biophys Acta. 1990 Aug 27;1050(1-3):160-2 PMID: 2119810
  66. Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787-91 PMID: 2217212
  67. Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent on multimer formation mediated through a basic stretch of amino acids.
    Genes Dev. 1990 Aug;4(8):1357-64 PMID: 2227413
  68. Structural analysis of the interaction between the human immunodeficiency virus Rev protein and the Rev response element.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):683-7 PMID: 1992459
  69. Interleukin 4 promotes expression of mast cell ICAM-1 antigen.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3339-42 PMID: 1673030
  70. HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency.
    Cell. 1991 Apr 19;65(2):241-8 PMID: 2015625
  71. Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
    J Morphol. 1972 Feb;136(2):153-79 PMID: 4109871
  72. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  73. The use of Xenopus oocytes for the expression of cloned genes.
    Methods Enzymol. 1983;101:370-86 PMID: 6193395
  74. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  75. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III).
    Science. 1985 Jul 5;229(4708):69-73 PMID: 2990040
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.123.6.1309
Published
1993-12-00
Pages
1309-20
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2290910
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.123.6.1309 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: [email protected]

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