Skip to main content

Cyclophilin and Gag in HIV-1 Replication and Pathogenesis

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 374))

Abstract

The gag gene products perform many functions in the retroviral life cycle. Recent work suggests that specific binding of HIV-1 Gag to the cellular proteins known as the cyclophilins is necessary for viral infectivity and perhaps of importance to the immunopathology associated with HIV infection. Cyclophilins are ubiquitous prolyl isomerases thought to function as chaperones. Members of this family of proteins are required for the immunosuppression induced by cyclosporin A and are suspected regulators of cellular activation pathways. Here we review the functions of the gag proteins, what is known about the Gag-cyclophilin interaction, and the possible relevence of this interaction for HIV-1 replication and pathogenesis.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aldrovandi, G. M., G. Feuer, L. Gao, B. Jamieson, M. Kristeva, I. S. Y. Chen and J. A. Zack. 1993. The SCID-hu mouse as a model for HIV-1 infection. Nature. 363:732–736.

    Article  PubMed  CAS  Google Scholar 

  2. Allan, J. S. 1992. Viral evolution and AIDS. J. NIH Res. 4:51–54.

    Google Scholar 

  3. Ameisen, J. C. and A. Capron. 1991. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol. Today. 12:102–105.

    CAS  Google Scholar 

  4. Anderson, S. K., S. Gallinger, J. Roder, J. Frey, H. A. Young and J. R. Ortaldo. 1993. A cyclophilin-related protein involved in the function of natural killer cells. Proc. Natl. Acad. Sci. USA. 90:542–546.

    Article  PubMed  CAS  Google Scholar 

  5. Andrieu, J.-M., P. Even, A. Venet, J.-M. Tourani, M. Stern, W. Lowenstein, C. Audroin, D. Eme, D. Masson, H. Sors, D. Israel-Biet and K. Beldjord. 1988. Effects of cyclosporin on T-cell subsets in human immunodeficiency virus disease. Clin. Immunol. Immunopathol. 46:181–198.

    Article  Google Scholar 

  6. Arthur, L. O., J. W. Bess, R. C. Sowder, R. E. Benveniste, D. L. Mann, J.-C. Chermann and L. E. Henderson. 1992. Cellular proteins bound to immunodeficiency viruses: Implications for pathogenesis and vaccines. Science. 258:1935–1938.

    Article  PubMed  CAS  Google Scholar 

  7. Banda, N. K., J. Bernier, D. K. Kurahara, R. Kurrle, N. Haigwood, R.-P. Sekaly and T. H. Finkel. 1992. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J. Exp. Med. 176:1099–1106.

    Article  PubMed  CAS  Google Scholar 

  8. Bell, K. D., O. Ramilo and E. S. Vitetta. 1993. Combined use of an immunotoxin and cyclosporine to prevent both actvated and quiescent peripheral blood T cells from producing type 1 human immunodeficiency virus. Proc. Natl. Acad. Sci. USA. 90:1411–1415.

    Article  PubMed  CAS  Google Scholar 

  9. Bergsma, D. J., C. Eder, M. Gross, H. Kersten, D. Sylvester, E. Appelbaum, D. Cusimano, G. P. Livi, M. M. McLaughlin, K. Kasyan, W. P. Prichett, M. J. Bossard, M. Brandt and M. A. Levy. 1991. The cyclophilin multigene family of peptidyl-prolyl isomerases. J. Biol. Chem. 266:23204–23214.

    PubMed  CAS  Google Scholar 

  10. Bierer, B. E., G. Hollander, D. A. Fruman and S. J. Burakoff. 1993. Cyclosporin A and FK506: molecular mechanisms of immunosuppression and probes for transplantation biology. Curr. Opin. Immunol. 5:763–773.

    Article  PubMed  CAS  Google Scholar 

  11. Bonyhadi, M. L., L. Rabin, S. Salimi, D. A. Brown, J. Kosek, J. M. McCune and H. Kaneshima. 1993. HIV induces thymus depletion in vivo. Nature. 363:728–732.

    Article  PubMed  CAS  Google Scholar 

  12. Bowerman, B., P. O. Brown, J. M. Bishop and H. E. Varmus. 1989. A nucleoprotein complex mediates the integration of retroviral DNA. Gene Dev. 3:469–478.

    Article  PubMed  CAS  Google Scholar 

  13. Bram, R. J., D. T. Hung, P. K. Martin, S. L. Schreiber and G. Crabtree. 1993. Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: Role of calcineurin-binding and cellular location. Mol. Cell. Biol. 13:4760–4769.

    CAS  Google Scholar 

  14. Bryant, M. and L. Ratner. 1990. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc. Natl. Acad. Sci. USA. 87:523–527.

    Article  PubMed  CAS  Google Scholar 

  15. Bukrinsky, M. I., S. Haggerty, M. P. Dempsey, N. Sharova, A. Adzhubel, L. Spitz, P. Lewis, D. Goldfarb, M. Emerman and M. Stevenson. 1993. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 365:666–669.

    Article  PubMed  CAS  Google Scholar 

  16. Cacalano, N. A., B.-X. Chen, W. L. Cleveland and B. F. Erlanger. 1992. Evidence for a functional receptor for cyclosporin A on the surface of lymphocytes. Proc. Natl. Acad. Sci. USA. 89:4353–4357.

    Article  PubMed  CAS  Google Scholar 

  17. Cameron, P. U., M. Pope, S. Gezelter and R. M. Steinman 1994. Infection and apoptotic cell death of CD4+ T cells during an immune response to HIV-1-pulsed dendritic cells. Aids Res. Hum. Retro. 10:61–71.

    Article  CAS  Google Scholar 

  18. Clipstone, N. A. and G. R. Crabtree. 1992. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature. 357:695–697.

    Article  PubMed  CAS  Google Scholar 

  19. Colley, N., E. Baker, M. Stamnes and C. Zuker. 1991. The cyclophilin homolog ninaA is required in the secretory pathway. Cell. 67:255–263.

    Article  PubMed  CAS  Google Scholar 

  20. Delchambre, M., D. Gheysen, D. Thines, C. Thiriart, E. Jacobs, E. Verdin, M. Horth, A. Burny and F. Bex. 1989. The Gag precursor of simian immunodeficiency virus assembles into virus-like particles. EMBO J. 8:2653–2660.

    PubMed  CAS  Google Scholar 

  21. DesGroseillers, L. and P. Jolicoeur. 1983. Physical mapping of the Fv-1 tropism host range determinant of BALB/c murine leukemia viruses. J.Virol. 48:685–696.

    PubMed  CAS  Google Scholar 

  22. Durfee, T., K. Becherer, P.-L. Chen, S.-H. Yeh, Y. Yang, A. E. Kilburn, W.-H. Lee and S. J. Elledge. 1993. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 7:555–569.

    Article  PubMed  CAS  Google Scholar 

  23. Dutz, J. P., D. A. Fruman, S. J. Burakoff and B. E. Bierer. 1993. A role for calcineurin in degranulation of murine cytotoxic lymphocytes. J. Immunol. 150:2591–2598.

    PubMed  CAS  Google Scholar 

  24. Famet, C. M. and W. A. Haseltine. 1991. Determination of viral proteins present in the human immunodeficiency virus type 1 preintegration complex. J. Virol. 65:1910–1915.

    Google Scholar 

  25. Fields, S. and O. Song. 1989. A novel genetic system to detect protein-protein interactions. Nature. 340:245–246.

    Article  PubMed  CAS  Google Scholar 

  26. Fischer, G. and F. X. Schmid. 1990. The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell. Biochemistry. 29:2205–2212.

    Article  PubMed  CAS  Google Scholar 

  27. Fischer, G., B. Wittmann-Liebold, K. Lang, T. Kiefhaber and F. X. Schmid 1989. Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature. 337:476–478.

    Article  PubMed  CAS  Google Scholar 

  28. Franke, E. K., H. E.-H. Yuan, K. L. Bossolt, S. P. Goff and J. Luban. 1994. Specificity and sequence requirements for interactions between various retroviral Gag proteins. J. Virol. 68:5300–5305.

    PubMed  CAS  Google Scholar 

  29. Franke, E. K., H. E.-H. Yuan and J. Luban. 1994. Specific incorporation of Cyclophilin A into HIV-1 virions. Submitted.

    Google Scholar 

  30. Friedman, J. and I. Weissman. 1991. Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the absence of CsA. Cell. 66:799–806.

    Article  PubMed  CAS  Google Scholar 

  31. Fruman, D A, S J Burakoff and B. E. Bierer. 1994. Immunophilins in protein folding and inununosuppression. FASEB J. 8:391–400.

    PubMed  CAS  Google Scholar 

  32. Fruman, D. A., P. E. Mather, S. J. Burakoff and B. E. Bierer. 1992. Correlation of calcineurin phosphatase activity and programmed cell death in murine T cell hybridomas. Fur. J. Immunol. 22:2513–2517.

    CAS  Google Scholar 

  33. Garcia, V. and A. D. Miller. 1991. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature. 350:508–511.

    Article  PubMed  CAS  Google Scholar 

  34. Gaynor, R. B., M. D. Kuwabara, F. K. Wu, J. A. Garcia, D. Harrich, M. Briskin, R. Wall and D. S. Sigman. 1988. Proc. Natl. Acad. Sci. USA. 85:9406–9410.

    Article  CAS  Google Scholar 

  35. Gething, M.-J. and J. Sambrook. 1992. Protein folding in the cell. Nature. 355:33–45.

    Article  PubMed  CAS  Google Scholar 

  36. Gheysen, D., E. Jacobs, F. de Foresta, C. Thiriart, M. Francotte, D. Thines and M. DeWilde. 1989. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell. 59:103–112.

    Article  PubMed  CAS  Google Scholar 

  37. Gottlinger, H. G., T. Dorfman, E. A. Cohen and W. A. Haseltine. 1993. Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses. Proc. Natl. Acad. Sci. USA. 90:7381–7385.

    Article  PubMed  CAS  Google Scholar 

  38. Gottlinger, H. G., J. G. Sodroski and W. A. Haseltine. 1989. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci., USA. 86:5781–5785.

    Article  PubMed  CAS  Google Scholar 

  39. Groux, H., G. Torpier, D. Monte, Y. Mouton, A. Capron and J. Ameisen. 1992. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J. Exp. Med. 175:331–340.

    Article  PubMed  CAS  Google Scholar 

  40. Haendler, B., R. Hofer-Warbinek and E. Hofer. 1987. Complementary DNA for human T-cell cyclophilin. EMBO J. 6:947–950.

    PubMed  CAS  Google Scholar 

  41. Hahn, B. H. 1994. Viral genes and their products. 21–43. In Textbook of AIDS Medicine, ed. Broder, M. and Bolognesi. Williams and Wilkins., Baltimore.

    Google Scholar 

  42. Handschumacher, R., M. Harding, J. Rice and R. Drugge. 1984. Cyclophilin: A specific cytosolic binding protein for cyclosporin A. Science. 226:544–547.

    Article  PubMed  CAS  Google Scholar 

  43. Harding, M. W., R. E. Handschumacher and D. W. Speicher. 1986. Isolation and amino acid sequence of cyclophilin J Biol. Chem. 261:8547–8555.

    PubMed  CAS  Google Scholar 

  44. Harper, J. W., G. R. Adami, N. Wei, K. Keyomarsi and S. J. Elledge. 1993. The p21 Cdk-interacting protein Cipl is a potent inhibitor of Gl cyclin-dependent kinases. Cell. 75:805–816.

    Article  PubMed  CAS  Google Scholar 

  45. Hasel, K. W., J. R. Glass, M. Godbout and J. G. Sutcliffe. 1991. An endoplasmic reticulum-specific cyclophilin. Mol. Cell. Biol. 11:3484–3491.

    PubMed  CAS  Google Scholar 

  46. Hopkins, N., J. Schindler and R. Hynes. 1977. Six NB-tropic murine leukemia viruses derived from a B-tropic virus of BALB/c have altered P30. J Virol. 21:309–318.

    PubMed  CAS  Google Scholar 

  47. Hsu, H. W., P. Schwartberg and S. P. Goff. 1985. Point mutations in the p30 domain of the gag gene of Moloney leukemia virus. Virology. 142:211–214.

    Article  PubMed  CAS  Google Scholar 

  48. Imberti, L., A. Sottini, A. Bettinardi, M. Puoti and D. Primi. 1991. Selective depletion in HIV infection of T cells that bear specific T cell receptor VB sequences. Science. 254:860–862.

    Article  PubMed  CAS  Google Scholar 

  49. Iwabuchi, K., B. Li, P. Bartel and S. Fields. 1993. Use of the two-hybrid system to identify the domain of p53 involved in oligomerization. Oncogene. 8:1693–1696.

    PubMed  CAS  Google Scholar 

  50. Jain, J., P. G. McCaffrey, Z. Miner, T. K. Kerppola, J. N. Lamert, G. L. Verdine, T. Curran and A. Rao. 1993. The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature. 365:352–355.

    Article  PubMed  CAS  Google Scholar 

  51. Kaelin, W., D. Pallas, J. De Caprio, F. Kaye and D. Livingston. 1991. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 64:521–532.

    Article  PubMed  CAS  Google Scholar 

  52. Kappes, J. C., J. S. Parkin, J. A. Conway, J. Kim, C. G. Brouillette, G. M. Shaw and B. H. Hahn. 1993. Intracellular transport and virion incorporation of vpx requires interaction with other virus type-specific components. Virology. 193:222–233.

    Article  PubMed  CAS  Google Scholar 

  53. Karpas, A., M. Lowdell, S. Jacobson and F. Hill. 1992. Inhibition of human immunodeficiency virus and growth of infected T cells by the immunosuppressive drugs cyclosporin A and FK506. Proc. Natl. Acad. Sci. USA. 89:8351–8355.

    Article  PubMed  CAS  Google Scholar 

  54. Kestler, J. W., D. J. Ringler, K. Mori, D. L. Panicali, P. K. Sehgal, M. D. Daniel and R. C. Desrosiers. 1991. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 65:651–663.

    Article  PubMed  CAS  Google Scholar 

  55. Kieffer, L. J., T. W. Seng, W. Li, D. G. Osterman, R. E. Handschumacher and R. M. Bayney. 1993. Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. J. Biol. Chem. 268:12303–12310.

    PubMed  CAS  Google Scholar 

  56. Klimkait, T., K. Strebel, M. D. Hoggan, M. A. Martin and J. M. Orenstein. 1990. The human immunodeficiency virus type -specific protein Vpu is required for efficient virus maturation and release. J. Virol. 64:621–629.

    PubMed  CAS  Google Scholar 

  57. Kofron, J. L., P. Kuzmic, V. Kishore, E. Colon-Bonilla and D. H. Rich. 1991. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotmetric assay. Biochemistry. 30:6127–6134.

    Article  PubMed  CAS  Google Scholar 

  58. Koga, Y., M. Sasaki, H. Yoshida, H. Wigzell, G. Kimura and K. Nomoto. 1990. Cytopathic effect determined by the amount of CD4 molecules in human cell lines expressing envelope glycoprotein of HIV. J. Immunol 144:94–102.

    PubMed  CAS  Google Scholar 

  59. Kohl, N. E., E. A. Emini, W. A. Schleif, L. J. Davis, J. C. Heimbach, R. A. Dixon, E. M. Scolnick and I. S. Sigal. 1988. Active human immunodeficiency virus protease is required for viral infectivity. Proc. Natl. Acad. Sci. USA. 85:4686–4690.

    Article  PubMed  CAS  Google Scholar 

  60. Koletsky, A. J., M. W. Harding and R. E. Handschumacher. 1986. Cyclophilin: distribution and variant properties in normal and neoplastic tissues. J. Immunol 137:1054–1059.

    PubMed  CAS  Google Scholar 

  61. Lane, H., J. Depper, W. Greene, G. Whalen, T. Waldmann and A. Fauci. 1985. Qualitative analysis of immune function in patients with the acquired immunodeficiency syndrome. N Eng J Med. 313:79–84.

    Article  CAS  Google Scholar 

  62. Laurent-Crawford, A., B. Krust, S. Muller, Y. Riviere, M.-A. Rey-Cuille, J.-M. Bechet, L. Montagnier and A. Hovanessian. 1991. The cytopathic effect of HIV is associated with apoptosis. Virology. 185:829–839.

    Article  PubMed  CAS  Google Scholar 

  63. La allee, C., X. J. Yao, A. Ladha, H. Gottlinger, W. A. Haseltine and E. A. Cohen. 1994. Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles. J. Virol. 68:1926–1934.

    Google Scholar 

  64. Lilly, F. and T. Pincus. 1973. Genetic control of murine viral leukemogenesis. Adv. Cancer Res. 17:231–277.

    Article  Google Scholar 

  65. Linial, M. L. and A. D. Miller. 1990. Retroviral RNA packaging: sequence requirements and implications. Curr. Top. Microbiol. Immunol. 157:125–152.

    Article  PubMed  CAS  Google Scholar 

  66. Liu, J., M. Alber, T. Wandless, S. Luan, D. Alberg, P. Belshaw, P. Cohen, C. MacKintosh, C. Klee and S. Schreiber. 1992. Inhibition of T cell signaling by immunophilin-ligand complexes correlates with loss of calcineurin phosphatase activity. Biochem. 31:3896–3901.

    Article  CAS  Google Scholar 

  67. Lodish, H. and N. Kong. 1991. Cyclosporin A inhibits an initial step in folding of transferrin within the endoplasmic reticulum. J. Biol. Chem. 266:14835–14838.

    PubMed  CAS  Google Scholar 

  68. Lu, Y.-L., P. Spearman and L. Ratner. 1993. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions. J. Virol. 67:6542–6550.

    PubMed  CAS  Google Scholar 

  69. Luban, J., K. B. Alin, K. L. Bossolt, T. Humaran and S. P. Goff. 1992. Genetic assay for multimerization of retroviral gag polyproteins. J. Virol. 66:5157–5160.

    PubMed  CAS  Google Scholar 

  70. Luban, J., K. A. Bossolt, E. K. Franke, G. V. Kalpana and S. P. Goff. 1993. Human immunodeficiency virus type 1 gag protein binds to cyclophilins A and B. Cell. 73:1067–1078.

    Article  PubMed  CAS  Google Scholar 

  71. Luban, J. and S. Goff. 1991. Binding of human immunodeficiency virus type 1 (HIV-1) RNA to recombinant HIV-1 gag polyprotein. J. Virol. 65:3203–3212.

    PubMed  CAS  Google Scholar 

  72. Luban, J., C. Lee and S. P. Goff. 1993. Effect of linker insertion mutations in the human immunodeficiency virus type 1 gag gene on activation of viral protease expressed in bacteria. J. Virol. 67:3630–3634.

    PubMed  CAS  Google Scholar 

  73. Luria, S., I. Chambers and P. Berg. 1991. Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. Proc. Natl. Acad. Sci. USA. 88:5326–5330.

    Article  PubMed  CAS  Google Scholar 

  74. Mammano, E, A. Ohagen, S. Hoglund and H. G. Gottlinger. 1994. Role of the major homology region of human immunodeficiency virus type 1 in virion morphogenesis. J. Virol. In press.

    Google Scholar 

  75. McCaffrey, P. G., C. Luo, T. K. Kerppola, J. Jain, T. M. Badalian, A. M. Ho, E. Burgeon, W. S. Lane, J. N. Lambert, T. Curran, G. L. Verdine, A. Rao and P. G. Hogan. 1993. Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science. 262:750–754.

    Article  PubMed  CAS  Google Scholar 

  76. McKeon, F. 1991. When worlds collide: immunosuppressants meet protein phosphatases. Cell. 66:823–826.

    Article  PubMed  CAS  Google Scholar 

  77. Meyaard, L., S. Otto, R. Jonker, M. Mijnster, R. Keet and F. Miedema. 1992. Programmed death of T cells in HIV-1 infection. Science. 257:217–219.

    Article  PubMed  CAS  Google Scholar 

  78. Myers, G., K. Maclnnes and B. Korber. 1992. The emergences of simian/human immunodeficiency viruses. AIDS Res. Human Retrovir. 8:373.

    Article  CAS  Google Scholar 

  79. Nabel, G. and D. Baltimore. 1987. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 326:711–713.

    Article  PubMed  CAS  Google Scholar 

  80. O’Keefe, S. J., J. Tamura, R. L. Kincaid, M. J. Tocci and E. A. O’Neill. 1992. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature. 357:692–694.

    Article  PubMed  Google Scholar 

  81. Pal, R., M. S. Reitz Jr., E. Tschachler, R. C. Gallo, M. G. Sarnagadharan and F. D. M. Veronese. 1990. Myristylation of gag proteins of HIV-1 plays an important role in virus assembly. AIDS Res. Hum. Retroviruses. 6:721–730.

    Article  CAS  Google Scholar 

  82. Pantaleo, G., C. Graziosi and A. Fauci. 1993. The immunopathogenesis of human immunodeficiency virus infection. N. Engl. J. Med. 328:327–335.

    Article  PubMed  CAS  Google Scholar 

  83. Pantaleo, G., M. Vaccarezza, O. J. Cohen, R. H. Hohman and A. S. Fauci. Cyclosporin A suppresses HIV-1 infection in primary T lymphocytes acutely infected in vitro. IXth International Conference on AIDS. 246, 1993.

    Google Scholar 

  84. Park, J. and C. D. Morrow. 1992. The nonmyristylated Pr160gag-pol polyprotein of human immunodeficiency virus type 1 interacts with Pr55gag and is incorporated into viruslike particles. J. Virol. 66:6304–6313.

    PubMed  CAS  Google Scholar 

  85. Paxton, W., R. I. Connor and N. R. Landau. 1993. Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for p6 region of gag and mutational analysis. J. Virol. 67:7229–7237.

    PubMed  CAS  Google Scholar 

  86. Peng, C., B. Ho, T. Chang and N. Chang. 1989. Role of human immunodeficiency virus type 1 specific protease in core maturation and viral infectivity. J. Virol. 63:2550–2556.

    PubMed  CAS  Google Scholar 

  87. Price, E. R., L. D. Zydowsky, M. Jin, C. H. Baker, F. D. McKeon and C. T. Walsh. 1991. Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. Proc. Natl. Acad. Sci. USA. 88:1903–1907.

    Article  PubMed  CAS  Google Scholar 

  88. Ramsay, G. and M. J. Hayman 1980. Analysis of cells transformed by defective leukemia virus OK10: production of noninfectious particles and synthesis of Pr76gag and an additional 200,000-dalton protein. Virology. 106:71–81.

    Article  PubMed  CAS  Google Scholar 

  89. Rebai, N., G. Pantaleo, J. F. Demarest, C. Ciurli, H. Soudeyns, J. W. Adelsberger, M. Vaccarezza, R. E. Walker, R. P. Sekaly and A. S. Fauci. 1994. Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbation of specific V beta segments in CD4+ T cells of the virus-positive twins. Proc. Natl. Acad. Sci. USA. 91:1529–1533.

    Article  PubMed  CAS  Google Scholar 

  90. Rein, A., M. McClure, N. Rice, R. Luftig and A. Schultz. 1986. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus. Proc. Natl. Acad. Sci., USA. 83:7246–7250.

    Article  PubMed  CAS  Google Scholar 

  91. Rhee, S. S. and E. Hunter. 1987. Myristylation is required for intracellular transport but not for assembly of D-type retrovirus capsids. J. Virol. 61:1045–1053.

    PubMed  CAS  Google Scholar 

  92. Rosenwirth, B., A. Billich, R. Datema, P. Donatsch, F. Hammerschmid, R. Harrison, P. Hiestand, H. Jaksche, P. Mayer, P. Peichl, V. Quesniaux, F. Schatz, H.-J. Schuurman, R. Traber, R. Wenger, B. Wolff, G. Zenke and M. Zurini. 1994. Inhibition of HIV-1 replication by SDC NIM 811, a non-immunosuppressive cyclosporin A analogue. Antimicro. Agents Chemother. 38:1763–1772.

    Article  CAS  Google Scholar 

  93. Schreiber, S. L. and G. R. Crabtree. 1992. The mechanism of action of cyclosporin A and FK506. Immunology Today. 13:136–142.

    Article  PubMed  CAS  Google Scholar 

  94. Schultz, A. M. and A. Rein. 1989. Unmyristoylated Moloney murine leukemia virus Pr65gag is excluded from virus assembly and maturation events. J. Virol. 63:2370–2373.

    PubMed  CAS  Google Scholar 

  95. Schwartz, O., M. Alizon, J. M. Heard and O. Danos. 1994. Impairment of t cell receptor-dependent stimulation in CD4+ lymphocytes after contact with membrane-bound HIV-1 envelope glycoprotein. Virology. 198:360–365.

    Article  PubMed  CAS  Google Scholar 

  96. Schwarz, A., G. Offermann, F. Keller, I. Bennhold, J. L’Age-Stehr, P. H. Krause and M. J. Mihatsch. 1993. The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation - Data on four cases and review of the literature. Transplantation. 55:95–103.

    Article  PubMed  CAS  Google Scholar 

  97. Shearer, G. and M. Clerici. 1991. Early T-helper cell defects in HIV infection. AIDS. 5:245–253.

    Article  PubMed  CAS  Google Scholar 

  98. Shi, Y., B. M. Sahai and D. R. Green. 1989. Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes. Nature. 339:625–626.

    Article  PubMed  CAS  Google Scholar 

  99. Shields, A., O. N. Witte, E. Rothenberg and D. Baltimore. 1978. High frequency of aberrant expression of Moloney murine leukemia virus in clonal infections. Cell. 14:601–609.

    Article  PubMed  CAS  Google Scholar 

  100. Shioda, T. and H. Shibuta. 1992. Production of human immunodeficiency virus (HIV)-like particles from cells infected with recombinant vaccinia viruses carrying the gag gene of HIV. Virology. 175:139–148.

    Article  Google Scholar 

  101. Sigal, N. H., F. Dumont, P. Durette, J. J. Siekierka, L. Peterson, D. H. Rich, B. E. Dunlap, M. J. Staruch, M. R. Melino, S. L. Koprak, D. Williams, B. Witzel and J. M. Pisano. 1991. Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A? J. Exp. Med. 173:619–628.

    Article  PubMed  CAS  Google Scholar 

  102. Skowronski, J., D. Parks and R. Mariani. 1993. Altered T cell activaton and development in transgenic mice expressing the HIV-1 nef gene. EMBO J. 12:703–713.

    PubMed  CAS  Google Scholar 

  103. Smith, A. J., N. Srinivasakumar, M.-L. Hanunarskjold and D. Rekosh. 1993. Requirements for incorporation of Pr160gag-pol from human immunodeficiency virus type 1 into virus-like particles. J. Virol. 67:2266–2275.

    PubMed  CAS  Google Scholar 

  104. Smith, D. B. and K. S. Johnson. 1988. Single-step purification of polypeptides expressed in Excherichia coli as fusions with glutathione S-transferase. Gene. 67:31–40.

    Article  PubMed  CAS  Google Scholar 

  105. Sodroski, J., W. C. Goh, C. Rosen, K. Campbell and W. A. Haseltine. 1986. Role of the HTLV III/LAV envelope in syncytium formation and cytopathicity. Nature. 322:470–474.

    Article  PubMed  CAS  Google Scholar 

  106. Stamnes, M. A., S. L. Rutherford and C. S. Zuker. 1992. Cyclophilins: a new family of proteins involved in intracellular folding. Trends in Cell. Biol. 2:272–276.

    CAS  Google Scholar 

  107. Steinmann, B, P. Bruckner and A. Superti-Furga. 1991. cyclosporin A slows collagen triple-helix formation in vivo: Indirect evidence for a physiologic role of peptidyl-prolyl cis-trans-isomerase. J. Biol. Chem. 266:1299–1303.

    PubMed  CAS  Google Scholar 

  108. Strambio-de-Castillia, C. and E. Hunter. 1992. Mutational analysis of the major homology region of Mason-Pfizer monkey virus by use of saturation mutagenesis. J. Virol. 66:7021–7032.

    PubMed  CAS  Google Scholar 

  109. Strebel, K., T. Klimkait, F. Maldarelli and M. A. Martin. 1989. Molecular and biochemical analysis of human immunodeficiency virus type 1 vpu protein. J. Virol. 63:3784–3791.

    PubMed  CAS  Google Scholar 

  110. Sykes, K., M.-J. Gething and J. Sambrook. 1993. Proline isomerases function during heat shock. Proc. Natl. Acad. Sci. USA. 90:5853–5857.

    Article  PubMed  CAS  Google Scholar 

  111. Terai, C., R. Kornbluth, C. Pauza, D. Richman and D. Carson. 1991. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J. Clin. Invest. 87:1710–1715.

    Article  PubMed  CAS  Google Scholar 

  112. Thali, M., A. A. Bukovsky, E. Kondo, B. Rosenwirth, C. T. Walsh, J. Sodroski and H. G. Goettlinger. 1994. Specific association of cyclophilin A with human immunodeficiency virus type 1 virions. Submitted.

    Google Scholar 

  113. Tristem, M., C. Marshall, A. Karpas and F. Hill. 1992. Evolution of the primate lentiviruses: evidence from vpx and vpr. EMBO J. 11:3405–3412.

    CAS  Google Scholar 

  114. Vojtek, A. B., S. M. Hollenberg and J. A. Cooper. 1993. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 774:205–214.

    Article  Google Scholar 

  115. Wainberg, M., A. Dascal, N. Blain, L. Fitz-Gibbon, F. Boulerice, K. Numazaki and M. Tremblay. 1988. The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1. Blood. 72:1904–1910.

    PubMed  CAS  Google Scholar 

  116. Walsh, C. T., L. D. Zydowsky and F. D. McKeon. 1992. Cyclosporin A, the cyclophilin class of petidylprolyl isomerases, and blockade of T cell signal transduction. J. Biol. Chem. 267:13115–13118.

    PubMed  CAS  Google Scholar 

  117. Wang, C.-T. and E. Barklis. 1993. Assembly, processing, and infectivity of human immunodeficiency virus type 1 gag mutants. J. Virol. 67:4264–4273.

    PubMed  CAS  Google Scholar 

  118. Wang, T., P. K. Donahoe and A. S. Zervos. 1994. Specific interaction of type I receptors of the TGF- 3 family with the immunophilin FKBP-12. Science. 265:674–676.

    Article  PubMed  CAS  Google Scholar 

  119. Weinhold, K., H. Lyerly, S. Stanley, A. Austin, T. Matthews and D. Bolognesi. 1989. HIV-1 pg120-mediated immune suppression and lymphocyte destruction in the absence of viral infection. J. Immunol. 142:3091–3097.

    PubMed  CAS  Google Scholar 

  120. Weiss, R. A. 1989. Defective viruses to blame? Nature. 338:458.

    Article  PubMed  CAS  Google Scholar 

  121. Yu, X.-F., M. Matsuda, M. Essex and T.-H. Lee. 1990. Open reading frame vpr of simian immunodeficiency virus encodes a virion-associated protein. J. Virol. 64:5688–5693.

    PubMed  CAS  Google Scholar 

  122. Zervos, A., J. Gyuris and R. Brent. 1993. Mxil, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 72:223–232.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Franke, E.K., Luban, J. (1995). Cyclophilin and Gag in HIV-1 Replication and Pathogenesis. In: Andrieu, JM., Lu, W. (eds) Cell Activation and Apoptosis in HIV Infection. Advances in Experimental Medicine and Biology, vol 374. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1995-9_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1995-9_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5823-7

  • Online ISBN: 978-1-4615-1995-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics