1887

Abstract

. Dengue is an emerging arboviral disease caused by dengue virus (DENV). DENV belongs to the family and genus . No specific anti-DENV drugs are currently available.

. We investigated the antiviral activity of Brefeldin A (BFA) and Cytochalasin B (CB) against this infection. The drugs BFA and CB were used in the treatment of dengue-2 virus (DENV-2) infections in Vero cell cultures and in protection from lethality by post-challenge administration in Swiss mice. Viral load was quantified by qRT-PCR and plaque assay in Vero cell cultures, post-infection, treated or not with the drugs. Post-challenge drug levels were evaluated by survival analysis.

. Our results indicate that doses of 5 µg ml of BFA and 10 µg ml of CB are not toxic to the cells and induce a statistically significant inhibition of DENV-2 replication in Vero cells when compared to control. No BFA- or CB-treated mice survived the challenge with DENV-2.

. These data suggest that BFA and CB have an antiviral action against DENV-2 replication in Vero cell culture, but do not alter infected mice mortality.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.0.000041
2019-08-01
2024-05-06
Loading full text...

Full text loading...

/deliver/fulltext/acmi/1/6/acmi000041.html?itemId=/content/journal/acmi/10.1099/acmi.0.000041&mimeType=html&fmt=ahah

References

  1. Kuno G, Chang GJ, Tsuchiya KR, Karabatsos N, Cropp CB. Phylogeny of the genus flavivirus. J Virol 1998; 72:73–83
    [Google Scholar]
  2. Lindenbach BD, Rice CM. Fields Virology. In Knipe DM, Howley PM. (editors) Flaviviridae Replication, 4th edition. Philadelphia: Lippincott Williams & Wilkins; 2001 pp 991–1041
    [Google Scholar]
  3. Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988; 239:476–481 [View Article]
    [Google Scholar]
  4. Fonseca BAL, Figueiredo LTM, Em D. Dengue. In Focaccia Roberto. editor Em “ Tratado de infectologia ”, 3ª edição. 2005 pp 343–356
    [Google Scholar]
  5. Kuhn RJ, Zhang W, Rossmann MG, Pletnev SV, Corver J et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 2002; 108:717–725
    [Google Scholar]
  6. Guirakhoo F, Heinz FX, Mandl CW, Holzmann H, Kunz C. Fusion activity of flaviviruses: comparison of mature and immature (prM-containing) tick-borne encephalitis virions. J Gen Virol 1991; 72:1323–1329 [View Article]
    [Google Scholar]
  7. Lindenbach BD, Rice CM. Molecular biology of flaviviruses. Adv Virus Res 2003; 59:23–61
    [Google Scholar]
  8. Richman DD, Whitley RJ, Hayden FG. Flaviviruses. Clinical Virology, 2nd edition. Washington, D.C: 2002 pp 1103–1104
    [Google Scholar]
  9. Swaminathan S, Khanna N. Dengue: recent advances in biology and current status of translational research. Curr Mol Med 2009; 9:152–173 [View Article]
    [Google Scholar]
  10. Huerta V, Chinea G, Fleitas N, Sarría M, Sánchez J et al. Characterization of the interaction of domain III of the envelope protein of dengue virus with putative receptors from CHO cells. Virus Res 2008; 137:225–234 [View Article]
    [Google Scholar]
  11. Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets RL et al. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 1985; 229:726–733 [View Article]
    [Google Scholar]
  12. Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 1990; 44:649–688 [View Article]
    [Google Scholar]
  13. Uchil PD, Satchidanandam V. Architecture of the flaviviral replication complex. J Biol Chem 2003; 278:24388–24398 [View Article]
    [Google Scholar]
  14. Elshuber S, Allison SL, Heinz FX, Mandl CW. Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J Gen Virology 2003; 84:183–191 [View Article]
    [Google Scholar]
  15. Qiu Z, Tufaro F, Gillam S. Brefeldin A and monensin arrest cell surface expression of membrane glycoproteins and release of rubella virus. J Gen Virol 1995; 76:855–863 [View Article]
    [Google Scholar]
  16. Lippincott-Schwartz J, Yuan L, Tipper C, Amherdt M, Orci L et al. Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic. Cell 1991; 67:601–616 [View Article]
    [Google Scholar]
  17. Pelham HRB. Multiple targets for brefeldin A. Cell 1991; 67:449–451 [View Article]
    [Google Scholar]
  18. Doms RW, Russ G, Yewdell JW. Brefeldin A redistributes resident and itinerant Golgi proteins to the endoplasmic reticulum. J Cell Biol 1989; 109:61–72 [View Article]
    [Google Scholar]
  19. Chen SY, Matsuoka Y, Compans RW. Assembly and polarized release of punta toro virus and effects of brefeldin A. J Virol 1991; 6:1427–1439
    [Google Scholar]
  20. Weclewicz K, Kristensson K, Greenberg HB, Svensson L. The endoplasmic reticulum-associated VP7 of rotavirus is targeted to axons and dendrites in polarized neurons. J Neurocytol 1993; 22:616–626 [View Article]
    [Google Scholar]
  21. Mirazimi ALI, Bonsdorff CV, Svensson L. Effect of Brefeldin A on Rotavirus Assembly and Oligosaccharide Processing. Virology 1996; 217:554–563 [View Article]
    [Google Scholar]
  22. Iglesias NG, Mondotte JA, Byk LA, De Maio FA, Samsa MM et al. Dengue virus uses a non-canonical function of the host GBF1-Arf-COPI system for capsid protein accumulation on lipid droplets. Traffic 2015; 16:962–977 [View Article]
    [Google Scholar]
  23. Mackenzie JM, Westaway EG. Assembly and maturation of the Flavivirus kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 2001; 75:10787–10799 [View Article]
    [Google Scholar]
  24. Sreenivasan V, Ng KL, Ng ML, ML N. Brefeldin A affects West Nile virus replication in Vero cells but not C6/36 cells. J Virol Methods 1993; 45:1–17 [View Article]
    [Google Scholar]
  25. Bernstein HB, Compans RW. Sulfation of the human immunodeficiency virus envelope glycoprotein. J Virol 1992; 66:6953–6959
    [Google Scholar]
  26. Tamura G, Ando K, Suzuki S, Takatsuki A, Arima K. Antiviral activity of brefeldin A and verrucarin a. J Antibiot 1968; 21:160–161 [View Article]
    [Google Scholar]
  27. Sidhu GS, Singh AK, Raghunath PN, Sivaram S, Maheshwari RK. Brefeldin A inhibits the antiviral action of interferon against encephalomyocarditis virus. Virus Res 1996; 40:123–133 [View Article]
    [Google Scholar]
  28. Cooper JA. Effects of cytochalasin and phalloidin on actin. J Cell Biol 1987; 105:1473–1478 [View Article]
    [Google Scholar]
  29. Chu JJH, Choo BGH, Lee JWM, Ng ML, ML N. Actin filaments participate in West Nile (Sarafend) virus maturation process. J Med Virol 2003; 71:463–472 [View Article]
    [Google Scholar]
  30. Boulanger D, Skinner MA, Smith T. Morphogenesis and release of fowlpox virus. J Gen Virol 2000; 81:675–687 [View Article]
    [Google Scholar]
  31. Bohn W, Rutter G, Hohenberg H, Mannweiler K, Nobis P. Involvement of actin filaments in budding of measles virus: studies on cytoskeletons of infected cells. Virology 1986; 149:91–106 [View Article]
    [Google Scholar]
  32. Wang JL, Zhang JL, Chen W, Xu XF, Gao N et al. Roles of small GTPase Rac1 in the regulation of actin cytoskeleton during dengue virus infection. PLoS Negl Trop Dis 2010; 4:e809 [View Article]
    [Google Scholar]
  33. Acosta EG, Castilla V, Damonte EB. Functional entry of dengue virus into Aedes albopictus mosquito cells is dependent on clathrin-mediated endocytosis. J Gen Virol 2008; 89:474–484 [View Article]
    [Google Scholar]
  34. Mosso C, Galván-Mendoza IJ, Ludert JE, del Angel RM. Endocytic pathway followed by dengue virus to infect the mosquito cell line C6/36 HT. Virology 2008; 378:193–199 [View Article]
    [Google Scholar]
  35. Coombs K, Mann E, Edwards J, Brown DT. Effects of chloroquine and cytochalasin B on the infection of cells by Sindbis virus and vesicular stomatitis virus. J Virol 1981; 37:1060–1065
    [Google Scholar]
  36. Griffin JA, Compans RW. Effect of cytochalasin B on the maturation of enveloped viruses. J Exp Med 1979; 150:379–391 [View Article]
    [Google Scholar]
  37. Trendowski M, Mitchell JM, Corsette CM, Acquafondata C, Fondy TP. Chemotherapy with cytochalasin congeners in vitro and in vivo against murine models. Invest New Drugs 2015; 33:290–299 [View Article]
    [Google Scholar]
  38. Ghosh S, Ahrens WA, Phatak SU, Hwang S, Schrum LW et al. Association of filamin A and vimentin with hepatitis C virus proteins in infected human hepatocytes. J Viral Hepat 2011; 18:e568–e577 [View Article]
    [Google Scholar]
  39. Grose C, Klionsky DJ. Alternative autophagy, brefeldin A and viral trafficking pathways. Autophagy 2016; 12:1429–1430 [View Article]
    [Google Scholar]
  40. Russell PK, Nisalak A. Dengue virus identification by plaque reduction neutralization test. J. Immunol 196799–291
    [Google Scholar]
  41. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65:55–63 [View Article]
    [Google Scholar]
  42. Houng HSH, Chung-Ming Chen R, Vaughn DW, Kanesa-thasan N. Development of a fluorogenic RT-PCR system for quantitative identification of dengue virus serotypes 1–4 using conserved and serotype-specific 3′ noncoding sequences. J Virol Methods 2001; 95:19–32 [View Article]
    [Google Scholar]
  43. Trevan JW. The error of determination of toxicity. Proceedings of the Royal Society B: Biological Sciences 1927; 101:483–514 [View Article]
    [Google Scholar]
  44. Phillips LR, Supko JG, Malspeis L. Analysis of Brefeldin A in Plasma by Gas Chromatography with Electron Capture Detection. Anal Biochem 1993; 211:16–22 [View Article]
    [Google Scholar]
  45. Austin WL, Wind M, Brown KS. Differences in the toxicity and teratogenicity of cytochalasins D and E in various mouse strains. Teratology 1982; 25:11–18 [View Article]
    [Google Scholar]
  46. Anwyl R, Narahashi T. Action of colchicine and cytochalasin B on the acetylcholine receptor. Br J Pharmacol 1979; 65:483–488 [View Article]
    [Google Scholar]
  47. Raekiansyah M, Mori M, Nonaka K, Agoh M, Shiomi K et al. Identification of novel antiviral of fungus-derived brefeldin A against dengue viruses. Trop Med Health 2017; 45:32 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.0.000041
Loading
/content/journal/acmi/10.1099/acmi.0.000041
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error