Avaliação da atividade antiviral e imunomodulatória dos compostos polifenólicos quercetina e kaempherol no contexto da infecção pelo HTLV-1

Abstract

In this study, the citotoxicity and antiviral effect of quercetin and kaempherol was evaluated on a HTLV-1 positive cell line (MT-2). The results indicated an specific citotoxicity of drugs on MT-2 when compared to THP-1 and PBMC cells. The antiviral activity of drugs was verified by the evaluation of env and tax transcription and viral protein expression assessed by western assay. The data revealed that quercetin and kaempherol were able to inhibit gag-pol mRNA levels in different magnitudes. The drugs also were shown to inhibit Gag and Env protein expression in a dose-dependent manner. Atomic Force Microscopy images of MT-2 cell surface demonstrated evidence of profuse viral budding as well as cell-free particles of HTLV-1. The evidence of profuse viral budding is abolished in the presence of quercetin and kaempherol. Instead, enormous pores were found on cell membrane indicating cell death. This data demonstrate and confirm that MT-2 cells present cell death and imparment of viral multiplicity in the presence of in high concentrations of quercetin and kaempherol and we hypotesize that induction of apoptosis could be a mechanism by which they exert those effects. The immunomodulatory effect of quercetin was also evaluated showing that this drug is potent as a modulator of Th1 and Th2 responses by inhibiting IFN- γ, TNF and IL-10 and inducing IL-4 expression. At last, the PHA-proliferation of PBMC from HTLV-1-infected and uninfected persons was assessed after treatment with quercetin (100 μM), demonstrating that this drug could be useful in the imparment of virus spread by cell proliferation on HTLV-1-infected persons. By and large, our data suggest that quercetin is a potential imunommodulatory compound which enables its use for future studies that focus on finding treatment approaches for HTLV-1-related diseases.