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PMID: 8648689 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cyclophilin A is required for an early step in the life cycle of human immunodeficiency virus type 1 before the initiation of reverse transcription.

Journal of virology ·Vol. 70 ·No. 6 ·1996-06-00 ·Pages 3551-60

Braaten D, Franke EK, Luban J

Abstract

Cyclophilin A (CyPA) is incorporated into human immunodeficiency virus type 1 (HIV-1) virions via contact with the Gag polyprotein. Genetic or pharmacologic disruption of CyPA incorporation causes a quantitative reduction in virion infectivity with no discernible effects on virion assembly or on endogenous reverse transcriptase activity. Instead, the reduction of virion-associated CyPA is accompanied by a parallel, quantitative decrease in the initiation of viral DNA synthesis after infection of T cells. The infectivity of CyPA-deficient virions is not restored by pseudotyping with Env of amphotropic murine leukemia virus, demonstrating that CyPA is not required for the HIV-1-Env-CD4 interaction. These results indicate that CyPA is required for an early step in the HIV-1 life cycle following receptor binding and membrane fusion but preceding reverse transcription. CyPA is the first cellular protein other than the cell surface receptor shown to be required for an early event in the life cycle of a retrovirus.

MeSH Terms
Amino Acid Isomerases/physiology Base Sequence Carrier Proteins/physiology DNA, Viral/biosynthesis Gene Products, gag/metabolism HIV-1/physiology Humans Membrane Fusion Molecular Sequence Data Peptidylprolyl Isomerase Transcription, Genetic Virion/physiology Virus Assembly Virus Replication
Chemicals
Carrier Proteins DNA, Viral Gene Products, gag Amino Acid Isomerases Peptidylprolyl Isomerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Braaten D
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York 10032, USA.
Franke E K
Luban J
References (68)
68 references, click to expand
  1. 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
  2. Inhibition of human immunodeficiency virus and growth of infected T cells by the immunosuppressive drugs cyclosporin A and FK 506.
    Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8351-5 PMID: 1381509
  3. Inhibition of human immunodeficiency virus replication by nonimmunosuppressive analogs of cyclosporin A.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5381-5 PMID: 7777516
  4. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions.
    J Virol. 1993 Nov;67(11):6542-50 PMID: 8411357
  5. Properties of avian retrovirus particles defective in viral protease.
    J Virol. 1990 Oct;64(10):5076-92 PMID: 1697912
  6. Sequence and organization of the human mitochondrial genome.
    Nature. 1981 Apr 9;290(5806):457-65 PMID: 7219534
  7. Effect of linker insertion mutations in the human immunodeficiency virus type 1 gag gene on activation of viral protease expressed in bacteria.
    J Virol. 1993 Jun;67(6):3630-4 PMID: 8497070
  8. Selective extraction of polyoma DNA from infected mouse cell cultures.
    J Mol Biol. 1967 Jun 14;26(2):365-9 PMID: 4291934
  9. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus.
    Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246-50 PMID: 3489936
  10. Domains upstream of the protease (PR) in human immunodeficiency virus type 1 Gag-Pol influence PR autoprocessing.
    J Virol. 1995 Jun;69(6):3878-84 PMID: 7745738
  11. Linker insertion mutations in the human immunodeficiency virus type 1 gag gene: effects on virion particle assembly, release, and infectivity.
    J Virol. 1995 Feb;69(2):642-50 PMID: 7815527
  12. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
    J Virol. 1986 Aug;59(2):284-91 PMID: 3016298
  13. Determination of viral proteins present in the human immunodeficiency virus type 1 preintegration complex.
    J Virol. 1991 Apr;65(4):1910-5 PMID: 2002549
  14. Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus type 1 (HIV-1): interference with early and late events in HIV-1 replication.
    J Virol. 1995 Feb;69(2):814-24 PMID: 7815548
  15. Cyclophilins: a new family of proteins involved in intracellular folding.
    Trends Cell Biol. 1992 Sep;2(9):272-6 PMID: 14731520
  16. 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
  17. Cyclophilin: distribution and variant properties in normal and neoplastic tissues.
    J Immunol. 1986 Aug 1;137(3):1054-9 PMID: 3522735
  18. Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis.
    J Virol. 1993 Dec;67(12):7229-37 PMID: 8230445
  19. Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins.
    Virology. 1987 Jan;156(1):171-6 PMID: 3643678
  20. The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1.
    Blood. 1988 Dec;72(6):1904-10 PMID: 2904290
  21. Specific incorporation of cyclophilin A into HIV-1 virions.
    Nature. 1994 Nov 24;372(6504):359-62 PMID: 7969494
  22. Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4.
    Nature. 1988 Jul 14;334(6178):162-5 PMID: 3260353
  23. Mutations in gag proteins P12 and P15 of Moloney murine leukemia virus block early stages of infection.
    J Virol. 1984 Mar;49(3):909-17 PMID: 6608006
  24. Fv-1 restriction and its effects on murine leukemia virus integration in vivo and in vitro.
    J Virol. 1992 Oct;66(10):5959-66 PMID: 1326652
  25. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.
    Science. 1993 Mar 19;259(5102):1749-54 PMID: 8096089
  26. The role of thioredoxin in filamentous phage assembly. Construction, isolation, and characterization of mutant thioredoxins.
    J Biol Chem. 1986 Nov 15;261(32):14997-5005 PMID: 3533930
  27. Binding of human immunodeficiency virus type 1 (HIV-1) RNA to recombinant HIV-1 gag polyprotein.
    J Virol. 1991 Jun;65(6):3203-12 PMID: 2033671
  28. The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin.
    EMBO J. 1994 Oct 17;13(20):4886-95 PMID: 7957056
  29. Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 PMID: 7687060
  30. Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity.
    J Virol. 1990 Nov;64(11):5270-6 PMID: 2214018
  31. Point mutations in the P30 domain of the gag gene of Moloney murine leukemia virus.
    Virology. 1985 Apr 15;142(1):211-4 PMID: 2414902
  32. Induction of cell differentiation by human immunodeficiency virus 1 vpr.
    Cell. 1993 Feb 26;72(4):541-50 PMID: 8440020
  33. The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell.
    Biochemistry. 1990 Mar 6;29(9):2205-12 PMID: 2186809
  34. 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
  35. pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane.
    Cell. 1987 Jun 5;49(5):659-68 PMID: 3107838
  36. Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA.
    J Biol Chem. 1992 Aug 15;267(23):16460-6 PMID: 1644830
  37. Cyclophilin catalyzes protein folding in yeast mitochondria.
    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6319-23 PMID: 7603990
  38. HIV accessory proteins: leading roles for the supporting cast.
    Cell. 1995 Jul 28;82(2):189-92 PMID: 7628010
  39. Form, function, and use of retroviral gag proteins.
    AIDS. 1991 Jun;5(6):639-54 PMID: 1883539
  40. Retroviral RNA packaging: sequence requirements and implications.
    Curr Top Microbiol Immunol. 1990;157:125-52 PMID: 2394131
  41. Assembly, processing, and infectivity of human immunodeficiency virus type 1 gag mutants.
    J Virol. 1993 Jul;67(7):4264-73 PMID: 7685414
  42. A nucleoprotein complex mediates the integration of retroviral DNA.
    Genes Dev. 1989 Apr;3(4):469-78 PMID: 2721960
  43. Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions.
    J Virol. 1995 Apr;69(4):2451-61 PMID: 7884893
  44. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level.
    J Immunol. 1984 Jul;133(1):123-8 PMID: 6327821
  45. Requirements for incorporation of Pr160gag-pol from human immunodeficiency virus type 1 into virus-like particles.
    J Virol. 1993 Apr;67(4):2266-75 PMID: 8445731
  46. Protein folding in the cell.
    Nature. 1992 Jan 2;355(6355):33-45 PMID: 1731198
  47. Enzymatic recycling of clathrin from coated vesicles.
    Cell. 1986 Jul 4;46(1):5-9 PMID: 2872968
  48. Functional association of cyclophilin A with HIV-1 virions.
    Nature. 1994 Nov 24;372(6504):363-5 PMID: 7969495
  49. The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions.
    J Virol. 1992 Aug;66(8):4966-71 PMID: 1629961
  50. Proline isomerases function during heat shock.
    Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5853-7 PMID: 7685914
  51. 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
  52. Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog.
    Antimicrob Agents Chemother. 1994 Aug;38(8):1763-72 PMID: 7527198
  53. Genomes of murine leukemia viruses isolated from wild mice.
    J Virol. 1981 Sep;39(3):777-91 PMID: 6270351
  54. HIV infection does not require endocytosis of its receptor, CD4.
    Cell. 1988 Sep 9;54(6):865-74 PMID: 3261635
  55. Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B.
    Cell. 1993 Jun 18;73(6):1067-78 PMID: 8513493
  56. 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
  57. 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
  58. Construction and use of a safe and efficient amphotropic packaging cell line.
    Virology. 1988 Dec;167(2):400-6 PMID: 2462307
  59. Quantitation of human immunodeficiency virus type 1 infection kinetics.
    J Virol. 1993 Apr;67(4):2182-90 PMID: 8445728
  60. Murine leukemia virus maturation: protease region required for conversion from "immature" to "mature" core form and for virus infectivity.
    Virology. 1985 Sep;145(2):280-92 PMID: 2411050
  61. Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus.
    Virology. 1992 Aug;189(2):695-714 PMID: 1386485
  62. Mutational analysis of the major homology region of Mason-Pfizer monkey virus by use of saturation mutagenesis.
    J Virol. 1992 Dec;66(12):7021-32 PMID: 1279197
  63. The mechanism of action of cyclosporin A and FK506.
    Immunol Today. 1992 Apr;13(4):136-42 PMID: 1374612
  64. Role of the major homology region of human immunodeficiency virus type 1 in virion morphogenesis.
    J Virol. 1994 Aug;68(8):4927-36 PMID: 8035491
  65. The nonmyristylated Pr160gag-pol polyprotein of human immunodeficiency virus type 1 interacts with Pr55gag and is incorporated into viruslike particles.
    J Virol. 1992 Nov;66(11):6304-13 PMID: 1383561
  66. Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsids.
    J Virol. 1987 Apr;61(4):1045-53 PMID: 3493352
  67. Role of the matrix protein in the virion association of the human immunodeficiency virus type 1 envelope glycoprotein.
    J Virol. 1994 Mar;68(3):1689-96 PMID: 8107229
  68. Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles.
    J Virol. 1994 Mar;68(3):1926-34 PMID: 8107252
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1996-06-00
Pages
3551-60
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC190230
Subset
IM
Grants
NIAID NIH HHS · R01 AI036199 · United States
NIAID NIH HHS · AI36199 · United States
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