Analysis of genetic markers involved with infection of lymphoid organs by influenza A virus using reverse genetics

• Grant number: 19/04983-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): May 20, 2019
• Effective date (End): September 19, 2019
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Ítalo de Araújo Castro
• Supervisor: Daniel Roberto Perez
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Georgia, Athens (UGA), United States
• Associated to the scholarship: 15/25975-0 - Influenza virus infection of lymphoid tissues, BP.DR

Abstract

Influenza viruses cause more than two million annual episodes of seasonal acute respiratory infections (ARI) and approximately 500 thousand deaths worldwide. Evidence from literature indicates that, depending on virus strain and host immune status, infections by influenza A virus (IAV) may be asymptomatic and reach sites other than the respiratory tract. Our previous results indicated that IAV can productively infect human immune cells directly involved in the anti-viral response, such as T CD8 lymphocytes and B lymphocytes, from palatine tonsils and adenoids. Next Generation Sequencing (NGS) analysis indicated that IAV detected in tonsils presents polymerase segments signatures typical of defective interfering RNAs (DI-RNAs). Moreover, all 8 segments formed a cluster together, phylogenetically distant from viruses that circulated in the same period. Upon genetic analysis, a group of nonsynonymous mutations exclusive of viruses from human tonsils were detected in all proteins, which may be involved in the phylogenetic segregation observed. Also, we hypothesize that these group of mutations, especially in the polymerase complex and in the surface glycoproteins, may have some role in the infection of lymphoid tissues by IAV. With this project, we expect to gain insight into the biologic impact of these mutations in the IAV pathogenesis using NGS and reverse genetic strategies.