Deciphering immune biomarkers of HTLV-1 infection and clinical outcome

• Grant number: 21/12316-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2021
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Jorge Simao do Rosario Casseb
• Grantee: Sandy Vieira Teixeira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/07239-2 - Incidence, risk factors, and pathogenic mechanism of neurocognitive disorders (HAND) among HIV-1-infected subjects, AP.TEM

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-I) is the etiologic agent of two main diseases, HTLV-associated myelopathy (HAM) and adult T-cell leukemia (ATL). This human oncogenic retrovirus infects between 10 and 20 million worldwide, with more than 1 million carriers living in Brazil. Several mechanisms lead to the progression of the HTLV-1-associated disease, the first being the oncogenic properties of the viral proteins Tax and HBZ, in addition to the establishment of a pro-tumor / inflammatory microenvironment. The understanding of the immunological biomarkers of this infection will help in the prognosis of patients, contributing to better clinical treatment, in addition to enabling the direction of new therapeutic interventions in the future. Therefore, immune responses to occurrences during an HTLV-1 infection should be further investigated in asymptomatic carriers, ATL and AMH. The results obtained may represent an important determinant of disease manifestation. In addition to the proviral load being insufficient to predict disease progression, innate immune dysregulation may provide therapeutic biomarkers of HTLV-1-related diseases. General objective: to understand immunological biomarkers in HTLV-1 infection and in patients co-infected with HTLV-1/HIV-1 and clinical outcome. Specific objectives: a) determine the frequency of immune cells, as well as their ability to produce cytokines after stimulation; b) to investigate whether T cells, monocytes, dendritic cells (mDCs and pDC), and NK cells are still available, in particular after TLR7 and PMA-ionomycin stimulation; c) quantify the proviral load of each sample. (AU)