Gene Therapy for HIV and AIDS-Related Opportunistic Infections

  • Kolls Jay K. 

Abstract

Gene therapy was initially conceptualised as gene replacement treatment for genetic diseases, particularly diseases that are inherited in an autosomal recessive fashion and carry a significant morbidity, such as Cystic Fibrosis. However, as the field has expanded, it has taken advantage of the increasing knowledge base that there are genetic components to acquired disorders such as cancer, HIV infection and other infectious diseases. For example, those individuals that lack expression of the HIV chemokine co-receptor are resistant to HIV infection and progression of the disease to AIDS. Moreover, knowing the operative host defence mechanisms against certain pathogens may allow one to exploit these pathways for therapeutic purposes using gene transfer technology. This article will focus on the evolving strategies to use gene-based therapies in HIV infection, TB, and Pneumocystis carinii pneumonia.

Keywords

Toxicity Pneumonia Interferon Pseudomonas Rosen 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literature Cited

  1. 1.
    Baltimore D. Gene therapy. Intracellular immunization. Nature. 1988; 335:395–396.PubMedCrossRefGoogle Scholar
  2. 2.
    Gilboa E, Smith C. Gene therapy for infectious diseases: the AIDS model. Trends Genet. 1994; 10:139–144.PubMedCrossRefGoogle Scholar
  3. 3.
    Sullenger BA, Gallardo HF, Ungers GE, Gilboa E. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell. 1990; 63:601–608.PubMedCrossRefGoogle Scholar
  4. 4.
    Caruso M, Klatzmann D. Selective killing of CD4+ cells harboring a human immunodeficiency virus-inducible suicide gene prevents viral spread in an infected cell population. Proc Natl Acad Sci USA. 1992; 89:182–186.PubMedCrossRefGoogle Scholar
  5. 5.
    Lisziewicz J. TAR decoys and trans-dominant gag mutant for HIV-1 gene therapy. Antibiot Chemother. 1996; 48:192–197.PubMedGoogle Scholar
  6. 6.
    Marasco WA, LaVecchio J, Winkler A. Human anti-HIV-1 tat sFv intrabodies for gene therapy of advanced HIV-1- infection and AIDS. J Immunol Methods. 1999; 231:223–238.PubMedCrossRefGoogle Scholar
  7. 7.
    Escaich S, Kalfoglou C, Plavec I, Kaushal S, Mosca JD, Bohnlein E. RevM10-mediated inhibition of HIV-1 replication in chronically infected T cells. Hum Gene Ther. 1995; 6:625–634.PubMedCrossRefGoogle Scholar
  8. 8.
    Nabel GJ, Fox BA, Post L, Thompson CB, Woffendin C. A molecular genetic intervention for AIDS-effects of a transdominant negative form of Rev. Hum Gene Ther. 1994; 5(l):79–92.CrossRefGoogle Scholar
  9. 9.
    Woffendin C, Ranga U, Yang Z, Xu L, Nabel GJ. Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients. Proc Natl Acad Sci USA. 1996; 93:2889–2894.PubMedCrossRefGoogle Scholar
  10. 10.
    Morgan RA, Walker R. Gene therapy for AIDS using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant Rev protein genes to syngeneic lymphocytes in HIV-1 infected identical twins. Hum Gene Ther. 1996; 7:1281–1306.Google Scholar
  11. 11.
    Donahue RE, Bunnell BA, Zink MC, Metzger ME, Westro RP, Kirby MR, Unangst T, Clements JE, Morgan RA. Reduction in SIV replication in rhesus macaques infused with autologous lymphocytes engineered with antiviral genes. Nat Med. 1998; 4(2):181–186.PubMedCrossRefGoogle Scholar
  12. 12.
    Bauer G, Valdez P, Kearns K, Bahner I, Wen SF, Zaia JA, Kohn DB. Inhibition of human immunodeficiency virus-1 (HIV-1) replication after transduction of granulocyte colony-stimulating factor- mobilized CD34+ cells from HIV-1-infected donors using retroviral vectors containing anti-HIV-1 genes. Blood. 1997; 89:2259–2267.PubMedGoogle Scholar
  13. 13.
    An DS, Morizono K, Li QX, Mao SH, Lu S, Chen IS. An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication. J Virol. 1999; 73:7671–7677.PubMedGoogle Scholar
  14. 14.
    Dropulic B, Hermankova M, Pitha PM. A conditionally replicating HIV-1 vector interferes with wild-type HIV- 1 replication and spread. Proc Natl Acad Sci USA. 1996; 93:11103–11108.PubMedCrossRefGoogle Scholar
  15. 15.
    Bukovsky AA, Song JP, Naldini L. Interaction of human immunodeficiency virus-derived vectors with wild- type virus in transduced cells. J Virol. 1999; 73:7087–7092.PubMedGoogle Scholar
  16. 16.
    Boyer JD, Wang B, Ugen KE, Agadjanyan M, Javadian A, Frost P, Dang K, Carrano RA, Ciccarelli R, Coney L, Williams WV, Weiner DB. In vivo protective anti-HIV immune responses in non-human primates through DNA immunization. J Med Primatol. 1996; 25:242–250.PubMedCrossRefGoogle Scholar
  17. 17.
    Pottratz ST. Pneumocystis carinii interactions with respiratory epithelium. Semin Respir Infect. 1998; 13:323–329.PubMedGoogle Scholar
  18. 18.
    Beck JM, Warnock ML, Curtis JL, Sniezek MJ, Arraj-Peffer SM, Kaltreider HB, Shellito JE. Inflammatory Responses to Pneumocystis Carinii in Mice Selectively Depleted of Helper T Lymphocytes. Am J Respir Cell Mol Biol. 1991; 5:186–197.PubMedGoogle Scholar
  19. 19.
    Azoulay E, Parrot A, Flahault A, Cesari D, Lecomte I, Roux P, Saidi F, Fartoukh M, Bernaudin JF, Cadranel J, Mayaud C. AIDS-related Pneumocystis carinii pneumonia in the era of adjunctive steroids: implication of BAL neutrophilia. Am J Respir Crit Care Med. 1999; 160:493–499.PubMedGoogle Scholar
  20. 20.
    Furrer H, Egger M, Opravil M, Bernasconi E, Hirschel B, Battegay M, Telenti A, Vernazza PL, Rickenbach M, Flepp M, Malinverni R. Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. Swiss HIV Cohort Study. N Engl J Med. 1999; 340:1301–1306.PubMedCrossRefGoogle Scholar
  21. 21.
    Weverling GJ, Mocroft A, Ledergerber B, Kirk O, Gonzales-Lahoz J, d’Arminio MA, Proenca R, Phillips AN, Lundgren JD, Reiss P. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. EuroSIDA Study Group. Lancet. 1999; 353:1293–1298.PubMedCrossRefGoogle Scholar
  22. 22.
    Kolls JK, Habetz S, Shean MK, Vazquez C, Brown JA, Lei D, Schwarzenberger P, Ye P, Nelson S, Summer WR, Shellito JE. IFN-gamma and CD8+ T Cells Restore Host Defenses Against Pneumocystis carinii in Mice Depleted of CD4+ T Cells. J Immunol. 1999; 162:2890–2894.PubMedGoogle Scholar
  23. 23.
    Mandujano FJ, D’Souza NB, Nelson S, Summer WR, Beckerman RC, Shellito JE. Granulocyte-macrophage colony stimulating factor and Pneumocystis carinii pneumonia in mice. Am J Respir Crit Care Med. 1995. 151:1233–1238.PubMedGoogle Scholar
  24. 24.
    Tumbarello M, Tacconelli E, de Gaetano K, Ardito F, Pirronti T, Cauda R, Ortona L. Bacterial pneumonia in HIV-infected patients: analysis of risk factors and prognostic indicators. J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 18:39–45.PubMedCrossRefGoogle Scholar
  25. 25.
    Wallace JM, Hansen NI, Lavange L, Glassroth J, Browdy BL, Rosen MJ, Kvale PA, Mangura BT, Reichman LB, Hopewell PC. Respiratory disease trends in the Pulmonary Complications of HIV Infection Study cohort. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med. 1997; 155:72–80.PubMedGoogle Scholar
  26. 26.
    Twigg HL, III, Spain BA, Soliman DM, Bowen LK, Heidler KM, Wilkes DS. Impaired IgG production in the lungs of HIV-infected individuals. Cell Immunol. 1996; 170:127–133.PubMedCrossRefGoogle Scholar
  27. 27.
    Greenberger MJ, Kunkel SL, Strieter RM, Lukacs NW, Bramson J, Gauldie J, Graham FL, Hitt M, Danforth JM, Standiford TJ. IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. J Immunol. 1996; 157:3006–3012.Google Scholar
  28. 28.
    Jaffe HA, Buhl R, Mastangeli A, Holroyd KJ, Saltini C, Czerski D, Jaffe HS, Kramer S, Sherwin S, Crystal RG. Organ specific cytokine therapy. Local activation of mononuclear phagocytes by delivery of an aerosol of recombinant interferon-gamma to the human lung. J Clin Invest. 1991; 88:297–302.PubMedCrossRefGoogle Scholar
  29. 29.
    Lei D, Lancaster JR, Jr., Joshi MS, Nelson S, Stoltz D, Bagby GJ, Odom G, Shellito JE, Kolls JK. Activation of alveolar macrophages and lung host defenses using transfer of the interferon-gamma gene. Am J Physiol. 1997; 272:L852–L859.Google Scholar
  30. 30.
    Kolls JK, Lei D, Stoltz D, Zhang P, Schwarzenberger PO, Ye P, Bagby G, Summer WR, Shellito JE, Nelson S. Adenoviral-mediated interferon-gamma gene therapy augments pulmonary host defense of ethanol-treated rats. Alcohol Clin Exp Res. 1998; 22:157–162.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Kolls Jay K. 
    • 1
  1. 1.LSU Health Sciences Gene Therapy ProgramNew OrleansUSA

Personalised recommendations