Potencial anti-viral do composto terpênico miriadenolídeo para o retrovírus HTLV-1

Abstract

The HTLV-1 (Human T-lymphotropic virus 1) infection is intractable and endemic in many countries, having a worldwide distribution. This retrovirus can be considered a neglected public health problem and is the causative agent of Adult T-cell leukemia/lymphoma (ATL) and HTLVAssociated Myelopathy / Tropical Spastic Paraparesis - HAM / TSP, a degenerative/inflammatory disease. The myelopathy trigger debilitating manifestations in infected individuals, and are observed high rates of morbidity and mortality. The development of diseases related to HTLV-1 are largely driven by the activity of the viral regulatory protein Tax, which modulates the expression of viral and cellular genes, favoring the installation and aggravation of diseases related to this retrovirus. Considering the severity of the clinical presentation of individuals infected with HTLV-1, especially with regard to the slowly progressive disorder resulting from a chronic immune inflammation and the lack of effective treatment, it is necessary to search for potential drugs to be used in therapeutic approach. In this context, studies have demonstrated the potential of terpene compounds in the treatment of many syndromes, highlighting the diterpene labdane (AMY), which has immunomodulatory activity specially showed by the inhibited production of TNF-α, IL-12 and NO. In this study was evaluated the antiviral and immunomodulatory activity of the diterpene compound in cells permanently infected with HTLV-1. AMY reduced accumulation of viral RNA messengers encoding structural and nonstructural proteins, besides negative regulation of the viral proteins, especially p19 e gp46. Cells treated with AMY also showed modulation on the interferon type I pathway, and reduced the production of proinflammatory cytokine IL-6. The transmission electron microscopy, confocal and atomic force microscopy assays showed a reduction in the number of HTLV-1 particles in treated cells compared to mock cells, and a induced either a reduction in the viral biofilm which is required for cell to cell viral transmission.