Influenza A virus persistence in experimentally infected mouse tissues: the role of Il-10

• Grant number: 24/05889-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Felipe Rocha do Nascimento
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/26119-0 - Emerging and re-emerging viruses: biology, pathogenesis and prospection, AP.TEM

Abstract

Influenza A virus (IAV) is enveloped, with a segmented single-stranded RNA genome of negative polarity, which is immensely relevant to public health. It is estimated that IAV causes over one billion cases and 290 to 646 thousand deaths annually, in addition to occasional pandemics, with the strongest example being the Spanish flu of 1918. IAV causes respiratory symptoms, which can progress to pneumonia and severe systemic disease. The replicative cycle occurs in the cell nucleus, and transcription by the viral polymerase results in many point mutations, generating great genetic variability and the emergence of seasonal variants. We have previously demonstrated that IAV causes prolonged asymptomatic infection in human lymphomonocytic cells in secondary lymphoid tissues, but investigating the mechanisms necessary for such observation requires the use of an experimental mouse model, allowing for the use of knockout animals for genes involved in viral persistence. In the present Master's project, we will investigate the role of IL-10, the main anti-inflammatory cytokine, in preventing tissue damage in acute infection caused by excessive inflammation, and in chronic infection. IAV dispersal in tissues will be evaluated, with an emphasis on secondary lymphoid organs, lung damage, and the effects of IL-10 absence on the development of persistent IAV infection. Intra-host genetic variation and the accumulation of defective viral genomes will be assessed to gain knowledge about their role in altering tissue tropism and their role in the viral persistence process.