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: 22/03163-7
• Support Opportunities: Research Grants - Initial Project
• Start date: February 01, 2023
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Hebert Fabricio Culler
• Grantee: Hebert Fabricio Culler
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Carolina Rosadas de Oliveira ; Debora Levy ; Felipe Vieira Rodrigues Maciel ; Jorge Simao do Rosario Casseb ; Juliana Pereira ; Luís Alberto de Pádua Covas Lage ; Youko Nukui
• Associated scholarship(s): 23/18471-1 - 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, BP.IC; 23/18474-0 - 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, BP.IC; 23/09971-0 - 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 transmis, BP.MS

Abstract

HTLV-1 virus infection and the molecular mechanisms associated with lymphomagenesis in ATLL are scarce. Although it takes six decades of latent viral infection until the development of T lymphoproliferative neoplasia, there is no biological marker that can be used in the clinical and laboratory monitoring of asymptomatic carriers of HTLV-1. Carriers who acquired HTLV-1 via the vertical route are more prone to neoplastic transformation, however contagion by other routes such as sexuais and parenteral, which can also progress to the malignant process, are few investigated. 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 for the development of the ATLL leukemic clone. However, the genetic-cellular alterations that are involved in this process have not been elucidated. Therefore, this study was designed to evaluate the 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 acquired vertically, sexually, parenterally and patients with ATLL. We hope to generate results that contribute to a better understanding of the pathophysiology associated with HTLV-1 infection and transformation to ATLL. (AU)