Summary
To test the feasibility of gene therapy for AIDS patients, an animal model is needed to evaluate the efficacy and safety of this approach. Antiviral genes (encoding antisense RNA or viral protein) derived from Simian immunodeficiency virus (SIV) were efficiently targeted into CD4+ lymphocytes through retroviral-mediated gene transfer. After challenging with infectious viruses, the transduced lymphocytes that received antiviral genes were not only protected from SIV infection, but also from infection with HIV, for at least 25 days. Furthermore, little or no cytolytic effect (syncytium formation) was observed in the protected cells. These data demonstrated that SIV or HIV replication could be effectively blocked by antisense sequence(s) or negative dominant factors which were introduced into targeted cells through retroviral-mediated gene transfer.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Baltimore D (1988) Intracellular immunization. Nature 335: 395–396
Cepko C, Roberts BE, Mulligan RC (1984) Construction and application of a highly transmissible murine retrovirus shuttle vector. Cell 37: 1053–1062
Chakrabarti L, Guyader M, Alizon M, Daniel MD, Desrosier RC, Tiollais P, Sonigo P (1987) Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature 328: 543–547
Clavel F, Guetard D, Brun-Vezinet F, Chamaret S, Rey M, Santos-Ferreira MO, Laurent AG, Dauguet C, Kaltama C, Rouzioux C, Klatzmann D, Champalimaud JL, Montagnier L (1986) Isolation of a new human retrovirus from West African patients with AIDS. Science 233: 343–346
Daniel MD, Letvin NL, King NW, Kannagi M, Sehgal PK, Hunt RD, Kanki PJ, Essex M, Desrosiers RC (1985) Isolation of T-cell tropic HTLV-III-like retrovirus from macques. Science 228: 1201–1204
Daniel MD, Letvin NL, Segal PK, Schmidt DK, Silvia DP, Solomon KR, Hodi FS, Ringler DJ, Hunt RD, King NW, Desrosiers RC (1988) Prevalence of antibodies to three retroviruses in a capative colony of macaque antibodies to three retroviruses in a capative colony of macaque monkeys. Int J Cancer 41: 601–608
Daniel MD, Li Y, Naidu YM, Durda MJ, Schmidt DK, Troup CD, Silva DP, Mackey JJ, Kestler HW III, Sehgal PK, King NW, Ohta Y, Hayami M, Desrosiers RC (1988) Simian immunodeficiency virus from African Green monkeys. J Virol 63: 4123–4128
Desrosiers RC (1988) Simian immunodeficiency viruses. Annu Rev Microbiol 42: 607–625
Desrosiers RC, Wyand MS, Kodama T, Ringler DJ, Arthur LO, Sehgal PK, Letvin NL, King NW, Daniel MD (1989) Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci USA 86: 6353–6357
Eglitis MA, Kantoff PW, Gilboa E, Anderson WF (1985) Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science 230: 1395–1398
Eglitis MA, Kantoff PW, Jolly JD, Jones JB, Anderson WF, Lothrop CD Jr (1988) Gene transfer into hematopoietic progenitor cells from normal and cyclic hematopoietic dogs using retroviral vectors. Blood 71: 717–722
Evan LA, McHugh TM, Stites DP, Levy JA (1987) Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol 138: 3415–3418
Guild BC, Finer MH, Housman DE, Mulligan R (1988) Development of retrovirus vectors useful for expressing genes in cultured murine embryonal cells and hematopoietic cells in vivo. J Virol 62: 3795–3801
Gross-Bellard M, Oudet P, Chambon P (1972) Isolation of high-molecular weight DNA from mammalian cells. Eur J Biochem 36: 32
Joshi S, Brunschot AV, Asad S, Elst IVD, Read SE, Bernstein A (1991) Inhibition of human immunodeficiency virus type I multiplication by antisense and sense RNA expression. J Virol 65: 5524–5530
Kitagawa M, Lackner AA, Martfeld DJ, Gardner MB, Dandekar S (1991) Simian immunodeficiency virus infection of macaque bone marrow macrophages correlates with disease progression in vivo. Am J Pathol 138: 921–930
Laneuville P, Chang W, Kamel-Reid S, Fauser AA, Dick JE (1988) High-efficiency gene transfer and expression in normal human hematopoietic cells with retrovirus vectors. Blood 71: 811–814
Letvin NL, Daniel MD, Sehgal PK, Desrosiers RC, Hunt RD, Waldron LM, Mackey JJ, Schmidt DK, Chalifoux LV, King NW (1985) Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science 230: 71–73
Markowitz D, Goff S, Bank A (1988) Construction and use of a safe and efficient amphotropic packaging cell line. Virology 167: 400–406
Miller AD, Rosman GJ (1989) Improved retroviral vectors for gene transfer and expression. Biotechniques 7: 980–990
Murphy-Corb M, Martin LM, Davison-Fairburn B, Montelaro RC, Miller M, West M, Ohkawa S, Baskin GB, Zhang JY, Putney SD, Allison AC, Eppstein DA (1989) A formalin-inactivated whole SIV vaccine confers protection in macaques. Science 246: 1293–1297
Naidu YM, Kestler HW III, Li Y, Butler CV, Silva DP, Schmidt DK, Troup CD, Sehgal PK, Sonigo P, Daniel MD, Desrosiers RC (1988) Characterization of infectious molecular clones of Simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecular cloned SIVmac. J Virol 62: 4091–4096
Palmer TD, Hock RA, Osborne WRA, Miller AD (1987) Efficient retrovirus-mediated transfer and expression of a human adenosine deaminase gene in diploid skin fibroblasts from an adenosine deaminase-deficient human. Proc Natl Acad Sci USA 84: 1055–1059
Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR Jr, Pearson ML, Lautenberger JA, Papas TS, Ghrayeb J, Chang NT, Gallo R, Wong-Staal F (1985) Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313: 277–284
Regier DA, Desrosiers RC (1990) The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses 6: 1221–1231
Rhodes A, James W (1990) Inhibition of human immunodeficiency virus replication in cell culture by endogenously synthesized antisense RNA. J Gen Virol 71: 1965–1974
Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, Karson EM, Lotze MT, Yang JC, Topalian SL, Merina MJ, Culver K, Miller AD, Blaese RM, Anderson WF (1990) Gene transfer into humans — immunotherapy of patients with advanced melanoma, using tumour-infiltrating lymphocytes modified by retroviral gene transduction. New infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 323: 570–578
Saag MS, Hahn BH, Gibbons J, Li Y, Parks ES, Parks WP, Shaw GM (1988) Extensive variation of human immunodeficiency virus type 1 in vivo. Nature 334: 440–447
Sczakiel G, Pawlita M (1991) Inhibition of human immunodeficiency virus type 1 replication in human T cells stably expressing antisense RNA. J Virol 65: 468–472
Sczakiel G, Oppenlander M, Rittner K, Pawlita M (1992) Tat-and rev-directed antisense RNA expression inhibits and abolishes replication of human immunodeficiency virus type 1: a temporal analysis. J Virol 66: 5576–5581
Simmonds P, Balfe P, Peutherer JF, Ludlam CA, Bishop JO, Brown AJL (1990) Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol 64: 864–872
Tersmette M, Goede R, Al BJ, Winkel IN, Gruters RA, Cuypers HT, Huisman HG, Miedema F (1988) Differential syncytium-inducing capacity of human immunodeficiency virus isolate: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol 62: 2026–2032
Trono DM, Feinberg B, Baltimore D (1989) HIV-1 gag mutant can dominantly interfere with the replication of the wild-type virus. Cell 59: 113–120
Tung FYT, Abraham S, Sethna M, Hung SL, Sethna P, Hogue BG, Brian DA (1992) The 9-kDa hydrobphobic protein encoded at the 3′ end of the porcine transmissible gastroenteritis coronavirus genome is membrane-associated. Virology 186: 676–683
Tung FYT (1993) A 3.5 kbp cDNA encoding the peplomer gene of TGEV was subcloned into MNC vector under the control of cytomegalovirus early promoter (unpublished)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tung, F.Y.T., Daniel, M.D. Targeted inhibition of immunodeficiency virus replication in lymphocytes through retroviral mediated gene transfer. Archives of Virology 133, 407–421 (1993). https://doi.org/10.1007/BF01313779
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01313779