View More View Less
  • 1 Semmelweis University Institute of Medical Microbiology Budapest Hungary
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $784.00

Antiretroviral effect of thiolated nucleotide 4-thio-uridylate (S4UMP, designated as UD29) against human immunodeficiency virus type 1 (HIV-1) have been quantitatively determined in cell-based viral infectivity assays. In syntitium inhibition assay on MT-2 human T-cell line UD29 prevented cell fusion and formation of syntitia induced by HIV-1IIIB with IC50 values of 11.7 μg/ml. In a single-cycle viral infection assay (MAGI assay) UD29 proved to have a potent inhibitory effect against HIV-1IIIB on HeLaCD4-LTR/β-gal cells, which was dose dependent with IC50 values of 4.75 μg/ml and IC90 of 39.7 μg/ml. UD29 showed a most prominent antiviral effect when administered 30 min prior HIV-1 infection. As HIV entry requires thiol/disulfide exchange process, results suggest that reactive -SH group of enol-form of the thiolated nucleotide may interfere with the function of cell surface proteins. UD29 cannot penetrate into cells and may have an interactive role in redox processes active in viral entry.

  • Nagy, K., Albert, J., Bánhegyi, D. (1988): Isolation of HIV from Hungarian AIDS and ARC patients. Laboratóriumi Diagnosztika 15(4), 213–216 (1988). (in Hungarian)

    Bánhegyi D. , 'Isolation of HIV from Hungarian AIDS and ARC patients ' (1988 ) 15 Laboratóriumi Diagnosztika : 213 -216.

    • Search Google Scholar
  • Wittinghoff, E., Scheer, S., O’Malley, P., Colfax, G., Holmberg, S. D., Buchbinder, S. P.: Combination antiretroviral therapy and recent decline in AIDS incidence and mortality. J Infect Dis 179(3), 717–720 (1999).

    Buchbinder S. P. , 'Combination antiretroviral therapy and recent decline in AIDS incidence and mortality ' (1999 ) 179 J Infect Dis : 717 -720.

    • Search Google Scholar
  • Albert, J., Abrahamson, B., Nagy, K., Aurelius, E., Gaines, H., Nyström, G., Fenyö, E.-M.: Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS 4, 107–113 (1990).

    Fenyö E.-M. , 'Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera ' (1990 ) 4 AIDS : 107 -113.

    • Search Google Scholar
  • Cox, S., Rudén, U., Nagy, K., Albert, J., Sandström, E., Holmbergm V., Wahren B.: Serum levels and catabolism of 3′-azido-3′-deoxythymidine in vivo measured using a specific radioimmunoassay. J Virol Meth 30, 89–98 (1990).

    Wahren B. , 'Serum levels and catabolism of 3′-azido-3′-deoxythymidine in vivo measured using a specific radioimmunoassay ' (1990 ) 30 J Virol Meth : 89 -98.

    • Search Google Scholar
  • Nagy, K., Young, M., Baboonian, C., Merson, J., Whittle, P., Oroszlan, S.: Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in a single cycle of infection: evidence for a role of protease in the early phase. J Virol 68, 757–765 (1994).

    Oroszlan S. , 'Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in a single cycle of infection: evidence for a role of protease in the early phase ' (1994 ) 68 J Virol : 757 -765.

    • Search Google Scholar
  • Juhász, E., Ghidán, Á., Kemény, B., Nagy, K.: Emergence of antiretroviral drug resistance in therapy-naive HIV infected patients in Hungary. Acta Microbiol Immunol Hung 55(4), 383–394 (2008).

    Nagy K. , 'Emergence of antiretroviral drug resistance in therapy-naive HIV infected patients in Hungary ' (2008 ) 55 Acta Microbiol Immunol Hung : 383 -394.

    • Search Google Scholar
  • Kanizsai, S., Ghidán, Á., Ujhelyi, E., Bánhegyi, D., Nagy, K.: Monitoring of drug resistance in therapy-naive HIV infected patients and detection of African HIV subtypes in Hungary. Acta Microbiol Immunol Hung 57(1), 55–68 (2010).

    Nagy K. , 'Monitoring of drug resistance in therapy-naive HIV infected patients and detection of African HIV subtypes in Hungary ' (2010 ) 57 Acta Microbiol Immunol Hung : 55 -68.

    • Search Google Scholar
  • Nagy, K.: HIV pseudovirions assay for coreceptor selection and entry fitness. In Fust, G. (ed.), Proc. HIV Correlates, June 5–7, Budapest, 2007, p. 12.

  • Nisole, S., Saib, A.: Early steps of retrovirus replication cycle. Retrovirology I 9, 1–20 (2004).

    Saib A. , 'Early steps of retrovirus replication cycle ' (2004 ) 9 Retrovirology I : 1 -20.

  • Einfeld, D.: Maturation and assembly of retroviral glycoprotein. Curr Top Microbiol 214, 133–176 (1996).

    Einfeld D. , 'Maturation and assembly of retroviral glycoprotein ' (1996 ) 214 Curr Top Microbiol : 133 -176.

    • Search Google Scholar
  • Kemény, B., Nagy, K., Horváth, A.: CCR5 and SDF1 gene polymorphism in HIV-infected and healthy individuals in Hungary. Hung Venerol Arch 4(2–3), 89–92 (2000).

    Horváth A. , 'CCR5 and SDF1 gene polymorphism in HIV-infected and healthy individuals in Hungary ' (2000 ) 4 Hung Venerol Arch : 89 -92.

    • Search Google Scholar
  • Berger, E. A., Murphy, P. M., Farber, J. M.: Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease. Annu Rev Immunol 17, 657–700 (1999).

    Farber J. M. , 'Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease ' (1999 ) 17 Annu Rev Immunol : 657 -700.

    • Search Google Scholar
  • Kilby, J. M., Eron, J. J.: Novel therapies based on mechanism of HIV-1 cell entry. N Engl J Med 348, 2228–2238 (2003).

    Eron J. J. , 'Novel therapies based on mechanism of HIV-1 cell entry ' (2003 ) 348 N Engl J Med : 2228 -2238.

    • Search Google Scholar
  • Ryser, H. J., Levy, E. M., Mandel, R., DiSciullo, G. J.: Inhibition of human immunodeficiency virus infection by agents that interfere with thiol-disulfide interchange upon virus-receptor interaction. Proc Natl Acad Sci USA 91, 4559–4563 (1994).

    DiSciullo G. J. , 'Inhibition of human immunodeficiency virus infection by agents that interfere with thiol-disulfide interchange upon virus-receptor interaction ' (1994 ) 91 Proc Natl Acad Sci USA : 4559 -4563.

    • Search Google Scholar
  • Horváth, A., Beck, Z., Bardos, T. J., Dunn, J. A., Aradi, J.: Effect of the extent of thiolation and introduction of phosphorothioate internucleotide linkages on the anti-HIV activity of Suligovir [(s4dU)3 ]. Bioorg Med Chem Lett 16, 5321–5323 (2006).

    Aradi J. , 'Effect of the extent of thiolation and introduction of phosphorothioate internucleotide linkages on the anti-HIV activity of Suligovir [(s4dU)3 ] ' (2006 ) 16 Bioorg Med Chem Lett : 5321 -5323.

    • Search Google Scholar
  • Beck, Z., Kis, A., Berenyi, E., Kovacs, P., Fesüs, L.. Aradi, J.: 4-Thio-uridylate (UD29) interferes with the function of protein -SH and inhibits HIV replication in vitro. Pharmacol Reports 61, 343–347 (2009).

    Aradi J. , '4-Thio-uridylate (UD29) interferes with the function of protein -SH and inhibits HIV replication in vitro ' (2009 ) 61 Pharmacol Reports : 343 -347.

    • Search Google Scholar
  • Tõkés, S., Aradi, J.: (s4dU)35: A novel highly potent oligonucleotide inhibitor of the human immunodeficiency virus type1 reverse transcriptase. FEBS Letter 396, 43–46 (1996).

    Aradi J. , '(s4dU)35: A novel highly potent oligonucleotide inhibitor of the human immunodeficiency virus type1 reverse transcriptase ' (1996 ) 396 FEBS Letter : 43 -46.

    • Search Google Scholar
  • Horváth, A., Tõkés, S., Hartman, T., Watson, K., Turpin, J. A., Buckheit, Jr. R. W., Sebestyén, Z., Szöllõsi, J., Benkõ, I., Bardos, T. J., Dunn, J. A., Fésüs, L., Tóth, F. D., Aradi, J.: Potent inhibition of HIV-1 entry by Suligovir (s4dU)3. Virology 334, 214–223 (2005).

    Aradi J. , 'Potent inhibition of HIV-1 entry by Suligovir (s4dU)3 ' (2005 ) 334 Virology : 214 -223.

    • Search Google Scholar
  • Nagy, K., Clapham, P., Cheingsong-Popov, R., Weiss, R. A.: Human-T-cell leukemia virus type I: Induction of syncytia and inhibition by patients’ sera. Int J Cancer 32, 321–328 (1983).

    Weiss R. A. , 'Human-T-cell leukemia virus type I: Induction of syncytia and inhibition by patients’ sera ' (1983 ) 32 Int J Cancer : 321 -328.

    • Search Google Scholar
  • Clapham, P., Nagy, K., Cheingsong-Popov, R., Exley, M., Weiss, R. A.: Productive infection and cell-free transmission of human T-cell leukemia virus in a non-lymphoid cell line. Science 222, 1125–1127 (1983).

    Weiss R. A. , 'Productive infection and cell-free transmission of human T-cell leukemia virus in a non-lymphoid cell line ' (1983 ) 222 Science : 1125 -1127.

    • Search Google Scholar
  • Leonard, C., Spellman, M. W., Riddle, L., Harris, R., Thomas, J., Gregory, T. J.: Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem 265, 10373–10382 (1990).

    Gregory T. J. , 'Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells ' (1990 ) 265 J Biol Chem : 10373 -10382.

    • Search Google Scholar
  • Doms, R. W., Peipert, S. C.: Unwelcomed guests with master keys: How HIV uses chemokin receptors for cellular entry. Virology 235, 179–190 (1997).

    Peipert S. C. , 'Unwelcomed guests with master keys: How HIV uses chemokin receptors for cellular entry ' (1997 ) 235 Virology : 179 -190.

    • Search Google Scholar
  • Barbouche, R., Miquelist, R., Jones, I. M., Fenouillet, E.: Protein-disulphide isomerase-mediated reduction of two disulfide binds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion. J Biol Chemistry 278, 3131–3136 (2003).

    Fenouillet E. , 'Protein-disulphide isomerase-mediated reduction of two disulfide binds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion ' (2003 ) 278 J Biol Chemistry : 3131 -3136.

    • Search Google Scholar
  • Fenouillet, E., Barbouche, R., Courageot, J., Miquelis, R.: The catalytic activity of protein disulfide isomerase is involved in human immunodeficiency virus envelope-mediated membrane fusion after CD4 cell binding. J Infect Dis 183, 744–752 (2001).

    Miquelis R. , 'The catalytic activity of protein disulfide isomerase is involved in human immunodeficiency virus envelope-mediated membrane fusion after CD4 cell binding ' (2001 ) 183 J Infect Dis : 744 -752.

    • Search Google Scholar
  • Matthias, L. J., Yam, P. T., Jiang, X. M., Vandegraaff, N., Li, P., Poumbourios, P., Donoghue, N., Hogg, P. J.: Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1. Nat Immunol 3, 727–733 (2002).

    Hogg P. J. , 'Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1 ' (2002 ) 3 Nat Immunol : 727 -733.

    • Search Google Scholar
  • Ou, W., Silver, J.: Role of protein disulfide isomerase and other thiol-reactive proteins in HIV-1 envelope protein-mediated fusion. Virology 350, 406–417 (2006).

    Silver J. , 'Role of protein disulfide isomerase and other thiol-reactive proteins in HIV-1 envelope protein-mediated fusion ' (2006 ) 350 Virology : 406 -417.

    • Search Google Scholar
  • Markovic, I., Stanchev, T. S., Fields, K. H., Tiffany, L. J., Tomic, M., Weiss, C. D., Broder, C. C. et al.: Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry. Blood 103, 1586–1594 (2004).

    Broder C. C. , 'Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry ' (2004 ) 103 Blood : 1586 -1594.

    • Search Google Scholar
  • Wilen, C. B., Tilton, J. C., Doms, R. W.: Molecular mechanism of HIV entry. In Rossmann, M. G., Rao, V. B. (Eds), Advances in Experimental Medicine and Biology. Springer, 2012.

  • Szatmari, I., Tõkés, S., Dunn, C. B., Bardos, T., Aradi, J.: Modified telomeric repeat amplification protocol: A quantitative radioactive assay for telomerase without using electrophoresis. Anal Biochem 282, 80–88 (2000).

    Aradi J. , 'Modified telomeric repeat amplification protocol: A quantitative radioactive assay for telomerase without using electrophoresis ' (2000 ) 282 Anal Biochem : 80 -88.

    • Search Google Scholar
  • Tarkanyi, I., Horvath, A., Szatmari, I., Eizert, H., Vamosi, G., Damjanovich, S., Segal-Bendirdijan, E., Aradi, J.: Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homooligonucleotide. FEBS Lett 579, 1411–1416 (2005).

    Aradi J. , 'Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homooligonucleotide ' (2005 ) 579 FEBS Lett : 1411 -1416.

    • Search Google Scholar
  • Kanizsai, Sz., Juhász, E., Ghidán, Á., Aradi, J., Nagy, K.: Antiretroviral effect of poly-thiolated compounds as HIV entry inhibitors. Acta Microbiol Immunol Hung 56(3), Suppl. 2nd CEFORM, p. 57 (2009).

    Nagy K. , 'Antiretroviral effect of poly-thiolated compounds as HIV entry inhibitors ' (2009 ) 56 Acta Microbiol Immunol Hung : 57 -.

    • Search Google Scholar

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Oct 2020 3 0 0
Nov 2020 1 4 1
Dec 2020 0 0 0
Jan 2021 5 0 0
Feb 2021 0 0 0
Mar 2021 11 0 0
Apr 2021 1 0 0