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

病毒 mRNA 和蛋白质的减少以及形态发生改变的诱导揭示了拉布丹二萜多聚腺苷酸在体外的抗 HTLV-1 活性

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作者:Camila Pacheco Silveira Martins, Orlando Abreu Gomes, Marina Lobato Martins, Luciana Debortoli de Carvalho, Jaqueline Gontijo de Souza, Flavio Guimaraes Da Fonseca, Rodrigo Gonçalves Silva dos Santos, Margareth Spangler Andrade, Carlos Leomar Zani, Elaine Maria de Souza-Fagundes, Edel Figueiredo Bar

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.

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.

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%.

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