Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Aim: Despite the existence of an effective vaccine, measles infection is still frequent in many developing countries with reduced health infrastructure, and it is one of the major causes of child death globally. In the past decade numerous outbreaks have occurred in developed countries, giving a fresh impetus to antiviral research against measles virus. The aim of this study was to investigate the antiviral activity of the natural steroid hormone DHEA against measles virus and the role of the Raf/MEK/ERK signaling pathway in viral multiplication and DHEA's antiviral activity. Materials & methods: The antiviral activity of DHEA and two ERK modulators, UO126 and anisomycin, was determined using a virus yield reduction assay. Furthermore, we studied DHEA's virucidal activity and the viral multiplication step affected by the compound. The effect of virus infection on the Raf/MEK/ERK pathway and the activity of those compounds against measles virus spread and induced cytopathic effect were studied using western blot and indirect immunofluorescence. Results & conclusion: We found that DHEA and UO126 are active against measles virus and that they are able to diminish virus-induced cytopathic effects. Also, our study showed that early events in the viral multiplication cycle trigger ERK activation, suggesting that DHEA, a Raf/MEK/ERK modulator, may not exert its antiviral activity through the modulation of this pathway. Our results may provide a first step in the development of new antiviral agents against measles virus. © 2012 Future Medicine Ltd.

Registro:

Documento: Artículo
Título:DHEA inhibits measles virus through a mechanism independent of its ability to modulate the Raf/MEK/ERK signaling pathway
Autor:Torres, N.I.; Castilla, V.; Wachsman, M.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428, Buenos Aires, Argentina
Palabras clave:anisomycin; antiviral agents; DHEA; measles virus; Raf/MEK/ERK signaling pathway; UO126; 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; anisomycin; mitogen activated protein kinase 1; mitogen activated protein kinase 3; prasterone; Raf protein; ribavirin; virus antigen; adsorption; animal cell; antiviral activity; article; concentration response; drug cytotoxicity; drug mechanism; enzyme activation; enzyme phosphorylation; immunofluorescence; Measles virus; nonhuman; priority journal; signal transduction; Vero cell; virus inhibition; virus pathogenesis; virus replication; Western blotting; Measles virus
Año:2012
Volumen:7
Número:11
Página de inicio:1115
Página de fin:1125
DOI: http://dx.doi.org/10.2217/fvl.12.107
Título revista:Future Virology
Título revista abreviado:Future Virol.
ISSN:17460794
CAS:1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene, 109511-58-2; anisomycin, 22862-76-6; mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; prasterone, 53-43-0; ribavirin, 36791-04-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17460794_v7_n11_p1115_Torres

Referencias:

  • Racaniello, V., An exit strategy for measles virus (2011) Science, 334, pp. 1650-1651
  • Hilleman, M.R., Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications (2001) Vaccine, 20 (5-6), pp. 651-665. , DOI 10.1016/S0264-410X(01)00384-X, PII S0264410X0100384X
  • Plemper, R.K., Snyder, J.P., Measles control - Can measles virus inhibitors make a difference? (2009) Curr. Opin. Investig. Drugs, 10, pp. 811-820
  • Sabella, C., Measles: Not just a childhood rash (2010) Cleve. Clin. J. Med., 77, pp. 207-213. , Comprehensive analysis of the current knowledge of measles epidemiology, pathogenesis, vaccination and antiviral therapies
  • Duke, T., Mgone, C.S., Measles: Not just another viral exanthem (2003) Lancet, 361 (9359), pp. 763-773. , DOI 10.1016/S0140-6736(03)12661-X
  • Perry, R.T., Halsey, N.A., The clinical significance of measles: A review (2004) Journal of Infectious Diseases, 189 (SUPPL. 1), pp. S4-S16
  • Reuter, D., Schneider-Schaulies, J., Measles virus infection of the CNS: Human disease, animal models, and approaches to therapy (2010) Med. Microbiol. Immunol., 199, pp. 261-271
  • Muscat, M., Bang, H., Wohlfahrt, J., Measles in Europe: An epidemiological assessment (2009) Lancet, 373, pp. 383-389. , Evaluation of the epidemiological data from measles outbreaks in Europe
  • Wichmann, O., Hellenbrand, W., Sagebiel, D., Santibanez, S., Ahlemeyer, G., Vogt, G., Siedler, A., Van Treeck, U., Large measles outbreak at a German public school, 2006 (2007) Pediatric Infectious Disease Journal, 26 (9), pp. 782-786. , DOI 10.1097/INF.0b013e318060aca1, PII 0000645420070900000003
  • Measles once again endemic in the United Kingdom (2008) Euro Surveill., 13 (27), p. 18919
  • Barnard, D.L., Inhibitors of measles virus (2004) Antiviral Chemistry and Chemotherapy, 15 (3), pp. 111-119
  • Del Toro-Riera, M., Macaya-Ruiz, A., Raspall-Chaure, M., Tallada-Serra, M., Pasqual-Lopez, I., Roig-Quilis, M., Subacute sclerosing panencephalitis: Combined treatment with interferon alpha and intraventricular ribavirin (2006) Revista de Neurologia, 42 (5), pp. 277-281. , http://www.neurologia.com/pdf/Web/4205/u050277.pdf
  • Hosoya, M., Therapy and prognosis in subacute sclerosing panencephalitis (2007) Nippon Rinsho, 65, pp. 1483-1486
  • Roberts, S.S., Miller, R.K., Jones, J.K., The ribavirin pregnancy registry: Findings after 5 years of enrollment, 2003-2009. Births Defects Res (2010) A Clin. Mol. Teratol., 88, pp. 551-559
  • Shiffman, M.L., What future for ribavirin? (2009) Liver Int., 29, pp. 68-73
  • Mori, T., Nakamura, Y., Kato, J., Oral ribavirin therapy for lower respiratory tract infection of respiratory syncytial virus complicating bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation (2011) Int. J. Hematol., 93, pp. 132-134
  • Arlt, W., Dehydroepiandrosterone and ageing (2004) Best Practice and Research: Clinical Endocrinology and Metabolism, 18 (3), pp. 363-380. , DOI 10.1016/j.beem.2004.02.006, PII S1521690X04000077
  • Saad, F., Hoesl, C.E., Oettel, M., Fauteck, J.-D., Rommler, A., Dehydroepiandrosterone treatment in the aging male - What should the urologist know? (2005) European Urology, 48 (5), pp. 724-733. , DOI 10.1016/j.eururo.2005.06.020, PII S0302283805004215
  • Castilla, V., Ramírez, J., Coto, C.E., Plant and animal steroids a new hope to search for antiviral agents (2010) Curr. Med. Chem., 17, pp. 1858-1873
  • Kroboth, P.D., Salek, F.S., Pittenger, A.L., Fabian, T.J., Frye, R.F., DHEA and DHEA-S: A review (1999) Journal of Clinical Pharmacology, 39 (4), pp. 327-348. , DOI 10.1177/00912709922007903
  • Van Vollenhoven, R.F., Dehydroepiandrosterone for the treatment of systemic lupus erythematosus (2002) Expert Opin. Pharmacother., 3, pp. 23-31
  • Pedersen, N.C., North, T.W., Rigg, R., Reading, C., Higgins, J., Leutenegger, C., Henderson, G.L., 16α-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: Initial enhancement leading to long-term suppression (2003) Veterinary Immunology and Immunopathology, 94 (3-4), pp. 133-148. , DOI 10.1016/S0165-2427(03)00081-3
  • Acacio, B.D., Stanczyk, F.Z., Mullin, P., Saadat, P., Jafarian, N., Sokol, R.Z., Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men (2004) Fertility and Sterility, 81 (3), pp. 595-604. , DOI 10.1016/j.fertnstert.2003.07.035, PII S0015028203030127
  • Chang, C.C., Ou, Y.C., Raung, S.L., Chen, C.J., Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection (2005) J. Gen. Virol., 86, pp. 2513-2523
  • Binder, G., Weber, S., Ehrismann, M., Effects of dehydroepiandrosterone therapy on pubic hair growth and psychological well-being in adolescent girls and young women with central adrenal insufficiency: A double-blind, randomized, placebocontrolled Phase III trial (2009) J. Clin. Endocrinol. Metab., 94, pp. 1182-1190
  • Kasperska-Zajac, A.E., Brzoza, Z.K., Koczy-Baron, E., Jagodzinska, J., Dehydroepiandrosterone in therapy of allergic diseases (2009) Recent Pat. Inflamm. Allergy Drug Discov., 3, pp. 211-213
  • Maninger, N., Wolkowitz, O.M., Reus, V.I., Epel, E.S., Mellon, S.H., Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) (2009) Front. Neuroendocrinol., 30, pp. 65-91
  • Kokona, D., Charalampopoulos, I., Pediaditakis, I., Gravanis, A., Thermos, K., The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement (2012) Neuropharmacology, 62, pp. 2106-2117
  • Mortola, J.F., Yen, S.S.C., The effects of oral dehydroepiandrosterone on endocrinemetabolic parameters in postmenopausal women (1990) J. Clin. Endocrinol. Metab., 71, pp. 696-704
  • Dyner, T.S., Lang, W., Geaga, J., Golub, A., Stites, D., Winger, E., Galmarini, M., Jacobson, M.A., An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease (1993) Journal of Acquired Immune Deficiency Syndromes, 6 (5), pp. 459-465
  • Morales, A.J., Nolan, J.J., Nelson, J.C., Yen, S.S.C., Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age (1994) Journal of Clinical Endocrinology and Metabolism, 78 (6), pp. 1360-1367. , DOI 10.1210/jc.78.6.1360
  • Labrie, F., Luu-The, V., Labrie, C., Belanger, A., Simard, J., Lin, S.-X., Pelletier, G., Endocrine and intracrine sources of androgens in women: Inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) Endocrine Reviews, 24 (2), pp. 152-182. , DOI 10.1210/er.2001-0031
  • Liu, D., Iruthayanathan, M., Homan, L.L., Wang, Y., Yang, L., Wang, Y., Dillon, J.S., Dehydroepiandrosterone stimulates endothelial proliferation and angiogenesis through extracellular signal-regulated kinase 1/2-mediated mechanisms (2008) Endocrinology, 149 (3), pp. 889-898. , http://endo.endojournals.org/cgi/reprint/149/3/889, DOI 10.1210/en.2007-1125
  • Andrade, A.A., Silva, P.N.G., Pereira, A.C.T.C., De Sousa, L.P., Ferreira, P.C.P., Gazzinelli, R.T., Kroon, E.G., Bonjardim, C.A., The vaccinia virus-stimulated mitogen-activated protein kinase (MAPK) pathway is required for virus multiplication (2004) Biochemical Journal, 381 (2), pp. 437-446. , DOI 10.1042/BJ20031375
  • Sharma-Walia, N., Krishnan, H.H., Naranatt, P.P., Zeng, L., Smith, M.S., Chandran, B., ERK1/2 and MEK1/2 induced by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection (2005) Journal of Virology, 79 (16), pp. 10308-10329. , DOI 10.1128/JVI.79.16.10308-10329.2005
  • Lee, Y.J., Lee, C., Porcine reproductive and respiratory syndrome virus replication is suppressed by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway (2010) Virus Res., 152, pp. 50-58
  • Zhang, H., Feng, H., Luo, L., Zhou, Q., Luo, Z., Peng, Y., Distinct effects of knocking down MEK1 and MEK2 on replication of herpes simplex virus type 2 (2010) Virus Res., 150, pp. 22-27
  • Pleschka, S., RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade (2008) Biol. Chem., 389, pp. 1273-1282
  • Denizot, F., Lang, R., Rapid colorimetric assay for cell growth and survival (1986) J. Immunol. Methods, 89, pp. 271-277
  • Talarico, L.B., Castilla, V., Ramirez, J.A., Galagovsky, L.R., Wachsman, M.B., Synergistic in vitro interactions between (22S,23S)-3β-bromo- 5α, 22,23-trihydroxystigmastan-6-one and acyclovir or foscarnet against herpes simplex virus type 1 (2006) Chemotherapy, 52 (1), pp. 38-42. , DOI 10.1159/000090242
  • Romanutti, C., Bruttomesso, A.C., Castilla, V., Galagovsky, L.R., Wachsman, M.B., Antiadenovirus activity of epiandrosterone and dehydroepiandrosterone derivatives (2010) Chemotherapy, 56, pp. 158-165
  • Hansen, J.L., Moore, P.B., Steitz, T.A., Structures of five antibiotics bound at the peptidyl transferase center of the large ribosomal subunit (2003) Journal of Molecular Biology, 330 (5), pp. 1061-1075. , DOI 10.1016/S0022-2836(03)00668-5
  • Hazzalin, C.A., Le Panse, R., Cano, E., Mahadevan, L.C., Anisomycin selectively desensitizes signalling components involved in stress kinase activation and fos and jun induction (1998) Molecular and Cellular Biology, 18 (4), pp. 1844-1854
  • Dhawan, P., Bell, A., Kumar, A., Golden, C., Mehta, K.D., Critical role of p42/44(MAPK) activation in anisomycin and hepatocyte growth factor-induced LDL receptor expression: Activation of Raf-1/MEK- 1/p42/44(MAPK) cascade alone is sufficient to induce LDL receptor expression (1999) Journal of Lipid Research, 40 (10), pp. 1911-1919
  • Chang, N.-S., Schultz, L., Heath, J., Suppression of IκBα expression is necessary for c-jun N-terminal kinase-mediated enhancement of Fas cytotoxicity (2000) Biochemical and Biophysical Research Communications, 274 (1), pp. 4-10. , DOI 10.1006/bbrc.2000.3089
  • Favata, M.F., Horiuchi, K.Y., Manos, E.J., Daulerio, A.J., Stradley, D.A., Feeser, W.S., Van Dyk, D.E., Trzaskos, J.M., Identification of a novel inhibitor of mitogen-activated protein kinase kinase (1998) Journal of Biological Chemistry, 273 (29), pp. 18623-18632. , DOI 10.1074/jbc.273.29.18623
  • Robert, N., Cambridge, L., Hart, L.A., Stevens, D.A., Lindsay, M.A., Barnes, P.J., The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1β-dependent PGE2 release via mechanistically distinct processes (2000) British Journal of Pharmacology, 130 (6), pp. 1353-1361
  • Diallo, K., Loemba, H., Oliveira, M., Mavoungoua, D.D., Wainberg, M.A., Inhibition of human immunodeficiency virus type-1 (HIV-1) replication by immunor (IM28), a new analog of dehydroepiandrosterone (2000) Nucleosides, Nucleotides and Nucleic Acids, 19 (10-12), pp. 2019-2024
  • Mavoungou, D., Poaty-Mavoungou, V., Akoume, M.Y., Ongali, B., Mavoungou, E., Inhibition of human immunodeficiency virus type-1 (HIV-1) glycoprotein-mediated cell-cell fusion by immunor (IM28) (2005) Virol. J., 11, pp. 9-10
  • Acosta, E.G., Bruttomesso, A.C., Bisceglia, J.A., Wachsman, M.B., Galagovsky, L.R., Castilla, V., Dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit Junin virus replication in vitro (2008) Virus Res., 135, pp. 203-212
  • Torres, N.I., Castilla, V., Bruttomesso, A.C., In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 (2012) Antiviral Res., 95, pp. 37-48
  • Cai, Y., Liu, Y., Zhang, X., Suppression of coronavirus replication by inhibition of the MEK signaling pathway (2007) Journal of Virology, 81 (2), pp. 446-456. , DOI 10.1128/JVI.01705-06
  • Dawson, C.W., Laverick, L., Morris, M.A., Tramoutanis, G., Young, L.S., Epstein-Barr virus-encoded LMP1 regulates epithelial cell motility and invasion via the ERK-MAPK pathway (2008) Journal of Virology, 82 (7), pp. 3654-3664. , DOI 10.1128/JVI.01888-07
  • Andrieux, L., Langouet, S., Fautrel, A., Ezan, F., Krauser, J.A., Savouret, J.F., Guengerich, F.P., Guillouzo, A., Aryl Hydrocarbon Receptor Activation and Cytochrome P450 1A Induction by the Mitogen-Activated Protein Kinase Inhibitor U0126 in Hepatocytes (2004) Molecular Pharmacology, 65 (4), pp. 934-943. , DOI 10.1124/mol.65.4.934
  • Dokladda, K., Green, K.A., Pan, D.A., Hardie, D.G., PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway (2005) FEBS Letters, 579 (1), pp. 236-240. , DOI 10.1016/j.febslet.2004.11.084, PII S0014579304014814
  • Mankouri, J., Harris, M., Viruses and the fuel sensor: The emerging link between AMPK and virus replication (2011) Rev. Med. Virol., 21, pp. 205-212
  • Collisson, E.A., De, A., Suzuki, H., Gambhir, S.S., Kolodney, M.S., Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade (2003) Cancer Research, 63 (18), pp. 5669-5673
  • Clark, J.E., Sarafraz, N., Marber, M.S., Potential of p38-MAPK inhibitors in the treatment of ischaemic heart disease (2007) Pharmacology and Therapeutics, 116 (2), pp. 192-206. , DOI 10.1016/j.pharmthera.2007.06.013, PII S0163725807001507

Citas:

---------- APA ----------
Torres, N.I., Castilla, V. & Wachsman, M. (2012) . DHEA inhibits measles virus through a mechanism independent of its ability to modulate the Raf/MEK/ERK signaling pathway. Future Virology, 7(11), 1115-1125.
http://dx.doi.org/10.2217/fvl.12.107
---------- CHICAGO ----------
Torres, N.I., Castilla, V., Wachsman, M. "DHEA inhibits measles virus through a mechanism independent of its ability to modulate the Raf/MEK/ERK signaling pathway" . Future Virology 7, no. 11 (2012) : 1115-1125.
http://dx.doi.org/10.2217/fvl.12.107
---------- MLA ----------
Torres, N.I., Castilla, V., Wachsman, M. "DHEA inhibits measles virus through a mechanism independent of its ability to modulate the Raf/MEK/ERK signaling pathway" . Future Virology, vol. 7, no. 11, 2012, pp. 1115-1125.
http://dx.doi.org/10.2217/fvl.12.107
---------- VANCOUVER ----------
Torres, N.I., Castilla, V., Wachsman, M. DHEA inhibits measles virus through a mechanism independent of its ability to modulate the Raf/MEK/ERK signaling pathway. Future Virol. 2012;7(11):1115-1125.
http://dx.doi.org/10.2217/fvl.12.107