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A reduction of viral mRNA, proteins and induction of altered morphogenesis reveals the anti-HTLV-1 activity of the labdane-diterpene myriadenolide in vitro.

Martins CP, Gomes OA, Martins ML, de Carvalho LD, de Souza JG, Da Fonseca FG, dos Santos RG, Andrade MS, Zani CL, de Souza-Fagundes EM, Barbosa-Stancioli EF - BMC Microbiol. (2014)

Bottom Line: We demonstrated that this natural product was able to inhibit the expression of gag-pol mRNA and substantially reduced the expression of the structural proteins p19 and gp46.Comparison of treated and untreated cells shows that AMY alters both the morphology and the release of viral particles.We demonstrated that the labdane diterpene myriadenolide reduced the expression of the structural proteins and the budding of viral particles, besides induces altered morphogenesis of HTLV-1, conferring on AMY a new antiviral activity that may be useful for the development of new compounds with specific anti-HTLV-1 activity.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Virologia Básica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais, Brazil. cpsmartins@yahoo.com.br.

ABSTRACT

Background: Human T-lymphotropic virus 1 (HTLV-1) has been associated with leukemia/lymphoma (ATL) and myelopathy/tropical spastic paraparesis (HAM/TSP), in addition to other inflammatory diseases as well as infection complications. Therapeutic approaches for HTLV-1-related pathologies are limited. The labdane diterpene myriadenolide (AMY) is a natural product that exhibit biological activities, such as anti-inflammatory and antiviral activity as reported for HIV and herpesvirus.

Results: We demonstrated that this natural product was able to inhibit the expression of gag-pol mRNA and substantially reduced the expression of the structural proteins p19 and gp46. Comparison of treated and untreated cells shows that AMY alters both the morphology and the release of viral particles. The Atomic Force Microscopy assay showed that the AMY treatment reduced the number of particles on the cell surface by 47%.

Conclusion: We demonstrated that the labdane diterpene myriadenolide reduced the expression of the structural proteins and the budding of viral particles, besides induces altered morphogenesis of HTLV-1, conferring on AMY a new antiviral activity that may be useful for the development of new compounds with specific anti-HTLV-1 activity.

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Related in: MedlinePlus

Effect of myriadenolide on MT-2, Jurkat cells and PBMC viability. Cells were treated with 1.0, 0.01 or 0.0001 μM myriadenolide for 24 hours. Cellular viability was inferred by MTT assay. All assays were performed in triplicate in at least two independent experiments. CC – Cell Control (Mock sample without DMSO and AMY). Average values with standard errors (error bars) are presented (GraphPad Prism 5).
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Fig1: Effect of myriadenolide on MT-2, Jurkat cells and PBMC viability. Cells were treated with 1.0, 0.01 or 0.0001 μM myriadenolide for 24 hours. Cellular viability was inferred by MTT assay. All assays were performed in triplicate in at least two independent experiments. CC – Cell Control (Mock sample without DMSO and AMY). Average values with standard errors (error bars) are presented (GraphPad Prism 5).

Mentions: To determine AMY cytotoxicity, MT2, Jurkat cells and human PBMC were treated with 1.0, 0.01 or 0.0001 μM AMY for 24 hours and the assay results are the mean of three independent experiments. For human PBMCs, the assay was performed in triplicate and with peripheral blood obtained from eight individuals. As demonstrated in Figure 1, treatment with different concentrations of AMY did not induce a significant reduction of cell viability in any of the cell types evaluated, compared to the diluent control (DMSO, 0.005%), showing the safety of this compound for the cell types tested, including human PBMCs, used as a control for normal cells.Figure 1


A reduction of viral mRNA, proteins and induction of altered morphogenesis reveals the anti-HTLV-1 activity of the labdane-diterpene myriadenolide in vitro.

Martins CP, Gomes OA, Martins ML, de Carvalho LD, de Souza JG, Da Fonseca FG, dos Santos RG, Andrade MS, Zani CL, de Souza-Fagundes EM, Barbosa-Stancioli EF - BMC Microbiol. (2014)

Effect of myriadenolide on MT-2, Jurkat cells and PBMC viability. Cells were treated with 1.0, 0.01 or 0.0001 μM myriadenolide for 24 hours. Cellular viability was inferred by MTT assay. All assays were performed in triplicate in at least two independent experiments. CC – Cell Control (Mock sample without DMSO and AMY). Average values with standard errors (error bars) are presented (GraphPad Prism 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4302425&req=5

Fig1: Effect of myriadenolide on MT-2, Jurkat cells and PBMC viability. Cells were treated with 1.0, 0.01 or 0.0001 μM myriadenolide for 24 hours. Cellular viability was inferred by MTT assay. All assays were performed in triplicate in at least two independent experiments. CC – Cell Control (Mock sample without DMSO and AMY). Average values with standard errors (error bars) are presented (GraphPad Prism 5).
Mentions: To determine AMY cytotoxicity, MT2, Jurkat cells and human PBMC were treated with 1.0, 0.01 or 0.0001 μM AMY for 24 hours and the assay results are the mean of three independent experiments. For human PBMCs, the assay was performed in triplicate and with peripheral blood obtained from eight individuals. As demonstrated in Figure 1, treatment with different concentrations of AMY did not induce a significant reduction of cell viability in any of the cell types evaluated, compared to the diluent control (DMSO, 0.005%), showing the safety of this compound for the cell types tested, including human PBMCs, used as a control for normal cells.Figure 1

Bottom Line: We demonstrated that this natural product was able to inhibit the expression of gag-pol mRNA and substantially reduced the expression of the structural proteins p19 and gp46.Comparison of treated and untreated cells shows that AMY alters both the morphology and the release of viral particles.We demonstrated that the labdane diterpene myriadenolide reduced the expression of the structural proteins and the budding of viral particles, besides induces altered morphogenesis of HTLV-1, conferring on AMY a new antiviral activity that may be useful for the development of new compounds with specific anti-HTLV-1 activity.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Virologia Básica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais, Brazil. cpsmartins@yahoo.com.br.

ABSTRACT

Background: Human T-lymphotropic virus 1 (HTLV-1) has been associated with leukemia/lymphoma (ATL) and myelopathy/tropical spastic paraparesis (HAM/TSP), in addition to other inflammatory diseases as well as infection complications. Therapeutic approaches for HTLV-1-related pathologies are limited. The labdane diterpene myriadenolide (AMY) is a natural product that exhibit biological activities, such as anti-inflammatory and antiviral activity as reported for HIV and herpesvirus.

Results: We demonstrated that this natural product was able to inhibit the expression of gag-pol mRNA and substantially reduced the expression of the structural proteins p19 and gp46. Comparison of treated and untreated cells shows that AMY alters both the morphology and the release of viral particles. The Atomic Force Microscopy assay showed that the AMY treatment reduced the number of particles on the cell surface by 47%.

Conclusion: We demonstrated that the labdane diterpene myriadenolide reduced the expression of the structural proteins and the budding of viral particles, besides induces altered morphogenesis of HTLV-1, conferring on AMY a new antiviral activity that may be useful for the development of new compounds with specific anti-HTLV-1 activity.

Show MeSH
Related in: MedlinePlus