Abstract
The inhibitory effect of all-trans-retinoic acid (RA) on human immunodeficiency virus (HIV) replication upon infection was studied quantitatively using a novel bioassay system with a HTLV-I-carrying human T-cell line, MT-4. The results can be summarized as follows. (1) The appearance of HIV antigen was significantly reduced when the cells were treated with more than 1 μg/ml of the chemical after infection. When HIV specific plaque assay was performed to titrate the virus from the supernatant of culture treated with 10 μg/ml of RA no plaques were observed. (2) When RA was applied directly in the plaque assay, significant decrease of the number of plaques was discerned showing 68, 66, 47 and 16, at doses of 0.1, 1, 5, and 10 μg/ml of RA, while 102 plaques were formed in the control dish. (3) The appearance of cytopathic effects of MT-4 cells by HIV was more delayed in RA-treated cultures than in untreated cultures. (4) Concomitant treatment of the cells with 5 μg/ml of RA and various concentrations of suramin resulted in the more effective inhibition of HIV replication than suramin alone. (5) RA did not inhibit the reverse transcriptase activity (RT) of HIV directly. These data suggest that RA inhibits HIV replication by inducing an antiviral state in the cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauget C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871
Broder S, Yarchoan R, Collins JM, Lane HC, Markham PD, Klecker PW, Redfield RR, Mitsuya H, Hoth DF, Gelmann E, Groopman JE, Resnick L, Gallo RC, Myeres CE, Fauci AS (1985) Effect of suramin of HTLV-III/LAV infection presenting as Kaposi's sarcoma or AIDS-related complex: Clinical pharmacology and suppression of virus replication in vivo. Lancet 2:627–630
Fauci AS, Macher AM, Longo DL, Rook AH, Masur H, Gelmann EP (1984) Acquired immunodificiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med 100:92–106
Feorino PH, Kalyanaraman VS, Haverkos HW, Cabradilla CD, Warfield DT, Jaffe HW, Harrison AK, Gottlieb MS, Goldfinger D, Chermann JC, Barré-Sinoussi F, Speia TT, Mc Dougal JS, Curran JW, Montagnier L, Murphy PA, Francis D (1984) Lymphadenopathy associated virus infection of a blood donor-recipient pair with aquired immunodeficiency syndrom. Science 225:69–72
Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, Saxon A (1981) Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med 305:1425–1431
Harada S, Koyanagi Y, Yamamoto N (1985a) Infection of human T-lymphotropic virus type-I (HTLV-I)-bearing MT-4 cells with HTLV-III (AIDS virus): Chronological studies of early events. Virology 146:272–281
Harada S, Yoshiyama H, Yamamoto, N (1985b) Effect of heat and fresh human serum on the infectivity of human T-cell lymphotropic virus type III evaluated with new bio-assay systems. J Clin Microbiol 22:908–911
Koyanagi Y, Harada S, Yamamotot N (1986) Establishment of a high production system for AIDS retroviruses with a human T-leukemic cell line Molt-4. Cancer Letters 30:299–310
Levy JA, Hoffman AD, Kramer SM, Landies JA, Shimabukuro JM, Oshiro LS (1984) Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 225:868–871
Lotan R (1980) Effect of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochem Biophys Acta 605:33–91
McCormik JB, Getchell JP, Mitchel SW, Hicks DR (1984) Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes. Lancet 2:1367–1369
Mitsuya H, Broder S (1986) Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphoadenopathy-associated virus (HTLV-III/LAV) by 2′,3′-dideoxynucleosides. Proc Natl Acad Sci USA 83:1911–1915
Mitsuya H, Popovic M, Yarchoan R, Matsushita S, Gallo RC, Broder S (1984) Suramin protection of T-cell in vitro against infectivity and cytopathic effect of HTLV-III. Science 226:172–174
Mitsuya H, Weinhold KJ, Furman PA, Clair HS, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S (1985) 3′-azido-3′-deoxythymidine (BWA509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphoadenopathy-associated virus in vitro. Proc Natl Acad Sci USA 82:7096–7100
Nakashima H, Koyanagi Y, Harada S, Yamamoto N (1986a) Effect of HTLV-III on the macromolecular synthesis in HTLV-I carrying cell line, MT-4. Med Microbiol Immunol 175:325–334
Nakashima H, Koyanagi Y, Harada S, Yamamoto N (1986b) Quantitative evaluations of the effect of UV irradiation on the infectivity of HTLV-III (AIDS virus) with HTLV-I carrying cell line, MT-4. J Invest Dermatol 87:239–243
Nakashima H, Matsui T, Harada S, Kobayshi N, Matsuda A, Ueda T, Yamamoto N (1986c) Inhibition of replication and cytopathic effect of human T cell leymphotropic virus type III/lymphadenopathy-associated virus by 3′-azido-3′-deoxythymidine in vitro. Antimicrob Agents Chemother 30:933–937
Popovic M, Sarangadharan MG, Read E, Gallo RC (1984) Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500
Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR, Pearson ML, Lautenberger JA, Papas TS, Ghrayeb J, Chang NT, Gallo RC, Wong-Staal F (1985) Complete nucleotide sequences of the AIDS virus, HTLV-III. Nature 313:277–284
Sanchez-Pescador R, Powe MD, Barr PJ, Steimer KS, Stempien MM, Brown-Shimer SL, Gee WW, Renard A, Randolph A, Levy JA, Dina D, Luciw PA (1985) Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science 227:484–497
Sandstorm EG, Kaplan JC, Byington RE, Hirsch MS (1985) Inhibition of human T-cell lymphotropic virus type III in vitro by phosphonoformate. Lancet 1:1480–1482
Siegal FP, Lopez C, Hammer GS, Brown AE, Kornifield SJ, Gold J, Hassett J, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR, Piarham DM, Siegal M, Cunningham-Rundles S, Armstrong D (1981) Several acquired immunodeficiency in male homosexuals, manifestated by chronic perianal ulcerative herpes simplex lesions. N Engl J Med 305:1439–1444
Sporn MB, Roberts AB (1983) Role of retinoids in differentiation and carcinogenesis. Cancer Res 43:3034–3044
Strannegard O, Öberg B (1983) Antiviral drugs. In: Lycke E, Norrby E (eds) Textbook of medical virology. Butterworth, Kent, UK, pp 230–241
Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M (1985) Nucleotide sequence of the AIDS virus, LAV. Cell 40:9–17
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nakashima, H., Harada, S. & Yamamoto, N. Effect of retinoic acid on the replication of human immunodeficiency virus in HTLV-I-positive MT-4 cells. Med Microbiol Immunol 176, 189–198 (1987). https://doi.org/10.1007/BF00196686
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00196686