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PMID: 9275210 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 18 ·1997-09-02 ·Pages 9825-30

Gallay P, Hope T, Chin D, Trono D

Abstract

The karyophilic properties of the HIV-1 nucleoprotein complex facilitate infection of nondividing cells such as macrophages and quiescent T lymphocytes, and allow the in vivo delivery of transgenes by HIV-derived retroviral vectors into terminally differentiated cells such as neurons. Although the viral matrix (MA) and Vpr proteins have previously been shown to play important roles in this process, we demonstrate here that integrase, the enzyme responsible for mediating the integration of the viral genome in the host cell chromosome, can suffice to connect the HIV-1 preintegration complex with the cell nuclear import machinery. This novel function of integrase reflects the recognition of an atypical bipartite nuclear localization signal by the importin/karyopherin pathway.

MeSH Terms
Cell Differentiation Cell Division Cell Line HIV Infections/virology HIV-1/physiology Humans Integrases/physiology Karyopherins Neurons/pathology,virology Nuclear Proteins/physiology Signal Transduction Virus Replication
Chemicals
Karyopherins Nuclear Proteins Integrases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gallay P
The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099, USA.
Hope T
Chin D
Trono D
References (32)
32 references, click to expand
  1. Cell cycle-dependent activation of rous sarcoma virus-infected stationary chicken cells: avian leukosis virus group-specific antigens and ribonucleic acid.
    J Virol. 1972 Jul;10(1):82-7 PMID: 4339198
  2. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells.
    Nature. 1993 Oct 14;365(6447):666-9 PMID: 8105392
  3. Integration of murine leukemia virus DNA depends on mitosis.
    EMBO J. 1993 May;12(5):2099-108 PMID: 8491198
  4. Sequence and characterization of cytoplasmic nuclear protein import factor p97.
    J Cell Biol. 1995 Jul;130(2):265-74 PMID: 7615630
  5. HIV-1 infection of non-dividing cells.
    Nature. 1994 May 12;369(6476):107-8 PMID: 8192816
  6. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11382-8 PMID: 8876144
  7. Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins.
    Cell. 1995 Dec 1;83(5):683-92 PMID: 8521485
  8. Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection.
    J Virol. 1995 Jun;69(6):3949-54 PMID: 7745752
  9. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression.
    J Virol. 1989 Sep;63(9):3708-13 PMID: 2760980
  10. Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import.
    J Virol. 1996 Feb;70(2):1027-32 PMID: 8551560
  11. Nuclear targeting sequences--a consensus?
    Trends Biochem Sci. 1991 Dec;16(12):478-81 PMID: 1664152
  12. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes.
    Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6580-4 PMID: 1631159
  13. Intracellular oligonucleotide hybridization detected by fluorescence resonance energy transfer (FRET).
    Nucleic Acids Res. 1994 Feb 25;22(4):662-8 PMID: 8127715
  14. Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis.
    J Virol. 1995 Aug;69(8):5048-56 PMID: 7541845
  15. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector.
    Science. 1996 Apr 12;272(5259):263-7 PMID: 8602510
  16. HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase.
    Cell. 1995 Nov 17;83(4):569-76 PMID: 7585960
  17. Conserved sequences in the carboxyl terminus of integrase that are essential for human immunodeficiency virus type 1 replication.
    J Virol. 1996 Jan;70(1):651-7 PMID: 8523588
  18. The nuclear localization signal of the matrix protein of human immunodeficiency virus type 1 allows the establishment of infection in macrophages and quiescent T lymphocytes.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6992-6 PMID: 8041734
  19. Nuclear targeting of SV40 and adenovirus.
    Trends Cell Biol. 1996 May;6(5):189-95 PMID: 15157471
  20. Human immunodeficiency virus infection of cells arrested in the cell cycle.
    EMBO J. 1992 Aug;11(8):3053-8 PMID: 1322294
  21. Subcellular localization of avian sarcoma virus and human immunodeficiency virus type 1 integrases.
    J Virol. 1997 Jan;71(1):843-7 PMID: 8985428
  22. The role of nuclear import and export in influenza virus infection.
    Trends Cell Biol. 1996 Feb;6(2):67-71 PMID: 15157497
  23. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain.
    Cell. 1994 Mar 11;76(5):853-64 PMID: 8124721
  24. Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse transcriptase.
    J Virol. 1981 Apr;38(1):239-48 PMID: 6165830
  25. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus.
    J Virol. 1994 Jan;68(1):510-6 PMID: 8254763
  26. HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator.
    Cell. 1995 Feb 10;80(3):379-88 PMID: 7859280
  27. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 PMID: 8041786
  28. HIV-1 reverse transcription. A termination step at the center of the genome.
    J Mol Biol. 1994 Sep 2;241(5):651-62 PMID: 7520946
  29. Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases.
    Science. 1994 Dec 23;266(5193):1981-6 PMID: 7801124
  30. Requirement for cell division for initiation of transcription of Rous sarcoma virus RNA.
    J Virol. 1974 Sep;14(3):531-46 PMID: 4369144
  31. Phosphorylation of residue 131 of HIV-1 matrix is not required for macrophage infection.
    Cell. 1997 Jan 24;88(2):171-3; discussion 173-4 PMID: 9008157
  32. Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6156-60 PMID: 8016130
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.18.9825
Published
1997-09-02
Pages
9825-30
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23276
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.18.9825 PMC Full Text View journal details
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