Human respiratory syncytial virus (HRSV) causes from mild infections in the upper respiratory tract to severe infection in the lower respiratory tract and is the main etiologic agent of lower respiratory tract infection in newborns, an age group in which it is one of the main causes of mortality. Acute HRSV infection of infants causes bronchiolitis due to the cytopathology caused by the virus in the epithelial tissue, which triggers an immune-inflammatory response, with tissue necrosis and small airway obstruction. In addition to acute infection with cytolysis, HRSV can cause persistent infection in in vitro models, and our research group has shown the presence of apparently persistent HRSV in human lymphoid tissues. Furthermore, we already have unpublished data showing that HRSV can persist for at least 180 days in lymphoid, kidney, lung, and central nervous system (CNS) tissues of experimentally inoculated mice and, importantly, there was no persistence in knockout animals for IL-10. Therefore, this project aims to investigate mechanisms of HRSV persistence in C57Bl/6 mouse tissues, highlighting the role of IL-10 and the accumulation of defective viral genomes (DVGs). Male newborn C57Bl/6 mice - normal and IL-10 knockouts - will be inoculated intranasally and will be observed for 6 months. Groups of 4 animals will be euthanized at different times post infection, to determine viral load, antigens and DVGs by real-time RT-PCR, immunohistochemistry and in situ hybridization of different organs to determine viral location and infected cell types, and measurement of mRNA and IL-10 protein. Previously unpublished preliminary data, such as persistent infection of the CNS and kidneys, will be examined in depth in more details in this project.
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