Potential risk and protection factors involved in HTLV-1 vertical transmission

• Grant number: 19/25511-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2020
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Jorge Simao do Rosario Casseb
• Grantee: Gabriela da Silva Prates
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/06636-3 - Mechanism and risk factors involved in the mother-to-child transmission (MTCT) of HTLV-1 infection in Brazil, BE.EP.DR

Abstract

Vertical transmission of HTLV-1 occurs mainly through breastfeeding; however, new infections have been reported even with the infant deprived of breast milk. Others, in turn, have been breastfed for a prolonged period and remain HTLV-1 seronegative. Despite the possibility of intrafamilial transmission, offspring of the same offspring can be infected via the maternal-fetal (TMTF) route. The mechanisms by which the placenta is overcome and the virus is transmitted to the offspring are not yet known. Several operant immunoregulation mechanisms during pregnancy such as the generated inflammation and antiviral response are vital for understanding HTLV-1 congenital infection as well as HTLV-1 proviral loading and expression of ERVs in the placenta may favor transplacental transmission of the virus. Basic responses of high clinical and social impact may be obtained from this study. General objective: to investigate risk and protective factors for HTLV-1 vertical transmission. Specific objectives: a) to investigate the relationship between the mother's age at pregnancy, socioeconomic status and neurological status of the mother with the risk of congenital infection; b) check the presence of HTLV DNA and RNA in all placental cells, umbilical cord and breast milk; c) check IgG anti-HTLV immunoglobulin levels in the placenta, umbilical cord, mother's plasma, newborn's plasma (after 1 year of life) and colostrum; d) to investigate the relationship between expression of ERVs in placental and cord samples with the occurrence of congenital infection compared with placentas of HTLV seronegative individuals; e) relate HTLV-1 proviral load, proinflammatory activity (IFN-gamma, IL-2, IL-6 and IL-8, TNF-alpha, neopterin and anti-inflammatory, TGF-beta, IL-10 in the placenta and in plasma at the risk of congenital infection; f) evaluate the seroconversion rate of newborns whose mothers are infected by HTLV-1, born by cesarean section, and deprived of breast milk; g) evaluate the presence of HTLV in colostrum of infected mothers after freezing and controlled thermal heating. (AU)