Inhibition of HTLV-III Replication in Cell Cultures

  • P. S. Sarin
  • D. Sun
  • A. Thornton
  • Y. Taguchi
Part of the NATO ASI Series book series (NSSA, volume 120)


A human T-lymphotropic retrovirus (HTLV-III) has been identified as the etiological agent for acquired immune deficieny syndrome (AIDS) and AIDS related complex (ARC) (1–4). Various therapeutic approaches are currently being investigated to control the disease either with inhibitors of reverse transcriptase and virus replication or with a vaccine. HTLV-III is a cytopathic retrovirus which selectively infects T-helper cells and kills OKT4+ T helper cells resulting in immune suppression (1–5). HTLV-III contains an RNA directed DNA polymerase (reverse transcriptase) and buds from the cell membrane like other animal retroviruses (6,7). The replication of virus in the infected cells and further infection of uninfected cells with the newly produced virus can be interfered by chemotherapeutic agents that can attack the various steps in the replication cycle (Fig. 1) including virus attachment, reverse transcription, and DNA integration.


Hairy Cell Leukemia Virus Attachment Fludarabine Phosphate Rous Sarcoma Virus Replication Rauscher Murine Leukemia Virus 
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  1. 1.
    R.C. Gallo, S.Z. Salahuddin, M. Popovic, G.M. Shearer, M. Kaplan, B.F. Haynes, T.J. Palker, R. Redfield, J. Oleske, B. Safai, G. White, P. Foster, and P.D. Markham, Frequent detection and isolation of cytopathic retrovirus (HTLV-III) from patients with AIDS and at risk for AIDS. Science, 224: 500–503 (1984)PubMedCrossRefGoogle Scholar
  2. 2.
    P.S. Sarin, and R.C. Gallo, The involvement of human T-lymphotropic retroviruses in T cell leukemia and immune deficiency. Cancer Reviews, 1: 1–17 (1986).Google Scholar
  3. 3.
    P.S. Sarin, and R.C. Gallo, Human T-lymphotropic retroviruses in adult T-cell leukemia-lymphoma and acquired immune deficiency syndrome. J. Clin. Immunolog., 4: 415–423 (1984)CrossRefGoogle Scholar
  4. 4.
    R.C. Gallo, The human T cell leukemia/lymphotropic retroviruses (HTLV) family: past, present and future. Cancer Res. (Suppl.) 45: 4524–4533 (1985)Google Scholar
  5. 5.
    M.Popovic, M.G. Sarngadharan, E. Read, and R.C. Gallo, Detection, isolation and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and preAIDS. Science, 224: 497–500 (1974)CrossRefGoogle Scholar
  6. 6.
    P.S. Sarin, and R.C. Gallo, RNA directed DNA polymerase, in: “MTP International Rev. Science” (Burton, K., edt.) Butterworths, London, vol. 6. pp. 219–254 (1974)Google Scholar
  7. 7.
    H.Temin, RNA directed DNA synthesis. Sci. American, 226: 25–33 (1972)CrossRefGoogle Scholar
  8. 8.
    A.B. Dalgleish, P.C. Beverley, P.R. Clapham, D. Crawford, M.F. Greaves, and R.A. Weiss, The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature, 312: 763–767 (1984)PubMedCrossRefGoogle Scholar
  9. 9.
    D.Klatzmann, E. Champagne, and S. Chamaret, T-lymphocyte T4 molecule behaves as the receptor for human retrovirus ‘LAV. Nature, 312: 767–768 (1984)PubMedCrossRefGoogle Scholar
  10. 10.
    R.Dolin, R.C. Reichman, H. Madore, R. Maynard, P. Linton, and J. Weber-Jones, A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. New Engl. J. Med., 307: 508–509 (1982)CrossRefGoogle Scholar
  11. 11.
    C.D. Richardson, A. Scheid, and P.W. Choppin, Specific inhibition of paramyxovirus and myxovirus replication by oligonucleotides with amino acid sequences similar to those at the N-termini of the Fl or HA2 viral polypeptides. Virology, 105: 205–222 (1985)CrossRefGoogle Scholar
  12. 12.
    P.S. Sarin, R.C. Gallo, D.I. Scheer, F. Crews, and A.S. Lippa, Effects of AL 721 on HTLV-III infectivity: a novel approach for the potential treatment of AIDS. New Engl. J. Med., 313: 1289–1290 (1985)PubMedCrossRefGoogle Scholar
  13. 13.
    P.Chandra, and P.S. Sarin, Selective inhibition of replication of the AIDS associated virus HTLV-III/LAV by synthetic D-penicillamine. Arzneimittelforschung (Drug Research) 36: 184–186 (1986)Google Scholar
  14. 14.
    C.Gurgo, Rifamycins as inhibitors of RNA and DNA polymerases, in: “Inhibitors of RNA and DNA polymerases. Intl. Encyl. of Pharmacol. Therapeutics” (P.S. Sarin, R.C. Gallo, edts.) Pergamon Press, New York, Section 103, pp. 235–247 (1980)Google Scholar
  15. 15.
    B.I.Milavetz, and W.A. Carter, Streptovaricins, in: “Inhibitors of RNA and DNA polymerases. Intl. Encycl. of Pharmacol. Therapeutics” (P.S. Sarin, R.C. Gallo, edts.) Pergamon Press, New York, Section 103, pp. 191–206 (1980)Google Scholar
  16. 16.
    P.M. Pitha, and J. Pitha, Polynucleotide analogs as inhibitors of RNA and DNA polymerases, in: “Intl. Encycl. of Pharmacol. and Therapeutics” (P.S. Sarin, R.C. Gallo, edts.) Pergamon Press, New York, Section 103, pp. 235–247 (1980)Google Scholar
  17. 17.
    P.Chandra, A. Vogel, and T. Gerber, Inhibitors of retroviral DNA polymerase. Their implication in treatment of AIDS. Cancer Res. (Suppl.), 45: 4677–4684 (1985)Google Scholar
  18. 18.
    P.S. Sarin, Y. Taguchi, D. Sun, A. Thornton, R.C. Gallo, and B. Oberg, Inhibition of HTLV-III/LAV replication by foscarnet. Biochem. Pharmacol., 34: 4075–4079 (1985)PubMedCrossRefGoogle Scholar
  19. 19.
    E.G. Sandstrom, J.C. Kaplan, R.E. Byington, and M.S. Hirsch, Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate. Lancet, 1: 1480–1482 (1985)PubMedCrossRefGoogle Scholar
  20. 20.
    B.Oberg, Control of cytomegalovirus infections with foscarnet, personal communicationGoogle Scholar
  21. 21.
    H.Mitsuya, M. Popovic, R. Yarchoan, S. Matsushita, R.C. Gallo, and S. Broder, Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science, 226: 172–174 (1984)PubMedCrossRefGoogle Scholar
  22. 22.
    S.Broder, R. Yarchoan, J.M. Collins, H.C. Lane, P.D. Markham, R.W. Klecker, R.R. Redfield, H. Mitsuya, D.F. Hoth, E. Gelmann, J.E. Groopman, L. Resnick, R.C. Gallo, C.E. Myers, and A.S. Fauci, Effects of suramin on HTLV-III/LAV infection presenting as Kaposi sarcoma or AIDS related complex: clinical pharmacology and suppression of virus replication in vivo. Lancet, 2: 627–630 (1985)PubMedCrossRefGoogle Scholar
  23. 23.
    H.Mitsuya, K.J. Weinhold, P.A. Furman, M.H. Clair, S.N. Lehrman, R.C. Gallo, D. Bolognesi, and S. Broder, 3’-azido-3’-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic retrovirus type III/lymphadenopathy associated virus in vitro. Proc. Natl. Acad. Sci. (USA), 82: 7096–7100 (1985)CrossRefGoogle Scholar
  24. 24.
    R.Yarchoan, R.W. Klecker, K.J. Weinhold, P.D. Markham, H.K. Lyerly, D.T. Durack, E. Gelmann, S.N. Lehrmann, R.M. Blum, D.W. Barry, G.M. Shearer, M.A. Fischl, H. Mitsuya, R.C. Gallo, J.M. Collins, D. Bolognesi, C.E. Myers, and S. Broder, Administration of 3’-azido-3’-deoxythymidine, an inhibitor of HTLV-III/LAV replication to patients with AIDS or AIDS related complex. Lancet, 1: 575–580 (1986)PubMedCrossRefGoogle Scholar
  25. 25.
    J.B. McCormick, J.P. Getchell, S.W. Mitchell, and D.R. Hicks, Ribavarin suppressed replication of lymphadenopathy associated virus in cultures of human adult T-lymphocytes. Lancet, 2: 1367–1369 (1984)PubMedCrossRefGoogle Scholar
  26. 26.
    W.Rozenbaum, D. Dormont, B. Spire, E. Vilmer, M. Gentilini, C. Griscelli, L. Montagnier, F. Barre-Sinoussi, and J.C. Chermann, Antimoniotungstate (HPA23) treatment of three patients with AIDS and one with prodrome. Lancet, 1: 450–451 (1985)PubMedCrossRefGoogle Scholar
  27. 27.
    P.S. Sarin, and R.C. Gallo, Human T-cell leukemia-lymphoma virus (HTLV). Prog. Hematol., 13: 149–161 (1983)PubMedGoogle Scholar
  28. 28.
    P.C. Zamecnik, and M.L. Stephenson, Inhibition of Rous sarcoma virus replication and transformation by a specific oligonucleotide. Proc. Natl. Acad. Sci. (USA), 75: 280–284 (1978)CrossRefGoogle Scholar
  29. 29.
    P.C. Zamecnik, J. Goodchild, Y. Taguchi, and P.S. Sarin, Inhibition of replication and expression of the human T-cell lymphotropic virus (HTLV-III) in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. Proc. Natl. Acad. Sci. (USA), in pressGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • P. S. Sarin
    • 1
  • D. Sun
    • 1
  • A. Thornton
    • 1
  • Y. Taguchi
    • 1
  1. 1.Laboratory of Tumor Cell BiologyNational Cancer InstituteBethesdaUSA

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