The role of IRF5 in the humoral response in emerging arboviroses with acute or chronic manifestations

Abstract

The Oropouche (OROV) and Mayaro (MAYV) viruses are neglected arboviruses, which circulate mainly in the Amazon region and have great potential for dissemination to new areas of Latin America or other regions of the globe. They are etiologic agents that cause exanthematous febrile illnesses that can progress to severe clinical cases, such as, neurological complications or chronic arthralgia. As a challenge, the search for the pathogenetic aspects of these diseases is necessary in order to discover factors related to the severity of symptoms, and markers that can assist in the development of new diagnostic methods and therapeutic approaches. Pathogen-associated pattern recognition (PAMPS) and the activation of innate immune response's components by antigen presenting cells are important for activation, cell proliferation, differentiation and the production of antibodies by B lymphocytes, thus helping to control infections. Components of this viral recognition pathway and type I interferon production by B lymphocytes may also impact the function and differentiation of these cells. In this direction, our group recently demonstrated that the absence of IRF-5, a transcription factor activated upon recognition of PAMPs, promotes neuroinvasion by OROV coupled with decreased levels of neutralizing antibodies in a murine model. Thus, we hypothesized that expression of this transcription factor in B lymphocytes is essential for proliferation and differentiation of antigen-specific cells, which is necessary for the control of primary viral infections. Thus, the objective of this project is to characterize the impact of IRF5 deletion in B lymphocytes for acute and chronic disease progression using CD19creIRF5f/f mice infected with OROV and MAYV viruses. To this end, we will analyze the tropism and kinetics of viral load, cytokine production, production of the different classes of specific antibodies, and B cell populations in animals infected with these viruses. (AU)