Infection of CD4 T lymphocytes by human respiratory syncytial virus: study of permissiveness, expression of viral genes and cellular repercussions

• Grant number: 20/10954-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2022
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Rosa Maria Mendes Viana
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 23/07268-0 - Infection of CD4 T lymphocytes by RSV: defective viral genome (DVG) formation and its pro-survival effects on the infected cells, BE.EP.DR

Abstract

Respiratory syncytial virus (HRSV) is the main agent of severe disease of the lower respiratory tract in children worldwide. This virus typically infects epithelial cells in the upper and lower respiratory tract, but studies conducted in the laboratory have shown by qPCR the presence of HRSV in tonsillar tissues and lymph nodes in patients without symptoms of respiratory infection. Previous studies by our group using serial immunohistochemistry and flow cytometry have found the presence of HRSV in CD4 + T lymphocytes in these tissues. In addition, previous results using infection of human CD4 + T lymphocytes of the A3.01 strain by HRSV, showed that the infection of these cells is not very productive, and that the inclusion bodies, although present, seem to be non-functional, thus resulting in low production of viral progeny. Thus, the present project aims to evaluate details of the virus-cell relationship in HRSV-infected CD4 + T lymphocytes, including their permissiveness, expression of viral genes and repercussions on cell viability and functions. Special attention will be paid to inclusion bodies and the role of viral protein M2-1, which is considered an important supporting factor in the process of viral polymerase. The findings obtained in the cell line A3.01 will be validated in primary cultures of human CD4 + T lymphocytes obtained by negative selection of lympho-hematopoietic tissues. (AU)