Dados do Trabalho

Título

HBZ and TAX role in the influence of FOXp3 regulation and inflammatory responses in people living with HTLV-1 with HAM/TSP

Introdução

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a disease characterized by chronic and progressive inflammation of the central nervous system (CNS). Viral proteins HBZ and TAX are recognized as important modulators of the immune response in HAM/TSP. The interaction between HBZ and FOXp3 has been shown to play a crucial role in regulating inflammation by regulatory T cells (Tregs), causing an unbalanced expression of several cytokines such as IL-10 and IFN-γ. All of this emphasizes the importance of understanding the interplay between viral and host factors in HAM/TSP pathogenesis.

Objetivo (s)

To investigate the role of HBZ and TAX expression on the induction of FOXp3 and inflammation in individuals with HAM/TSP.

Material e Métodos

This is a cross-sectional analytical study that enrolled people living with HTLV-1, including people with HAM/TSP and asymptomatic careers (AC), who are treated at the CHTLV of EBMSP, Salvador, Bahia, Brazil. Clinical and epidemiological data were collected, and blood samples were taken for the separation of PBMCs and extraction of DNA and RNA. The proviral load (PVL) was quantified by qPCR for each sample. The expression of HBZ, Tax, and host genes as IFNG, IL10, FOXP3, TNF, IL1B, CXCL10, CCL2, IL6, IL17A, IL4, IL18, IL23A, and GAPDH are being quantified by qPCR. The data obtained will be used to build a network using the HIT-BAY methodology, which integrates clinical and epidemiological data.

Resultados e Conclusão

Samples from 51 individuals were collected, and 47 of them were included in this study. Twenty were AC, nine were asymptomatic for HAM/TSP, seven were characterized as probable HAM/TSP, and 11 had definite HAM/TSP. Of the 47 individuals, 77% were women, with a median age of 56 years, and 51% self-declared as mixed race. The HAM/TSP group presented the highest PVL 30,422 copies of viral DNA/10⁶ cells (PVL median: 19,657 copies of viral DNA/10⁶ cells). The qPCR for mRNA expression analysis is being performed. It is expected that the quantitative analysis of gene expression will enable a better understanding of the virus-host interaction and facilitate the identification of important markers for HAM/TSP. These results may clarify HAM/TSP pathogenesis and identify genetic pathways that, when modulated, protect the host from the disease. Therefore, the results can be applied in the prevention of HAM/TSP and in the development of therapeutic measures.

Palavras-chave

HTLV-1, HAM/TSP, FOXp3, TAX, HBZ