Analysis of gene expression profile, immune signature, mutational landscape and pró-viral load of HTLV-1 in CD4+ memory stem T cells of asymptomatic carriers and patients with ATLL: comparative assessment between the different routes of viral transmission

• Grant number: 23/18474-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: December 31, 2025
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Hebert Fabricio Culler
• Grantee: Giulia Sales Guimarães
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/03163-7 - Analysis of gene expression profile, immune signature, mutational landscape and pró-viral load of HTLV-1 in CD4+ memory stem T cells of asymptomatic carriers and patients with ATLL: comparative assessment between the different routes of viral transmission, AP.PNGP.PI

Abstract

HTLV-1 virus infection and the molecular mechanisms associated with lymphomagenesis inATLL are scarce. Although it takes six decades of latent viral infection until the development ofT lymphoproliferative neoplasia, there is no biological marker that can be used in the clinical andlaboratory monitoring of asymptomatic carriers of HTLV-1. Carriers who acquired HTLV-1 viathe vertical route are more prone to neoplastic transformation, however contagion by other routessuch as sexuais and parenteral, which can also progress to the malignant process, are fewinvestigated. Recently, it has been shown that the HTLV-1 reservoir may be memory stem T-CD4+ cells (MTSC-CD4+) and, associated with cellular exhaustion, both would be triggers forthe development of the ATLL leukemic clone. However, the genetic-cellular alterations that areinvolved in this process have not been elucidated. Therefore, this study was designed to evaluatethe relationship between HTLV-1 infection and MTSC-CD4+in terms of quantity; cell exhaustion,proviral load and genomic-molecular profile in asymptomatic carriers of HTLV-1 acquiredvertically, sexually, parenterally and patients with ATLL. We hope to generate results thatcontribute to a better understanding of the pathophysiology associated with HTLV-1 infection andtransformation to ATLL.