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Morphogenetic analysis of the infection mechanisms of the USUV and its effects on neurogenesis in murine model

Abstract

In humans, by the third week of pregnancy, the formation of embryonic structures responsible for generating nervous tissue begins, and this process is crucial for the viability of the developing embryo. At this stage, embryonic cells undergo an intense period of proliferation and differentiation, which is controlled by finely regulated signaling. Any disturbance in these processes can lead to various damages to the fetus. In 2016 an unprecedented association between Zika virus infection in pregnant women and the occurrence of congenital malformations, especially microcephaly, was reported. This association led us to consider the existence of other flaviviruses with the same pathogenic potential, which was partially demostrated by recent literature. This becomes even more important since several climatic and socioeconomic worldwide changes seem to have potentiated the emergence of these arboroviral diseases. In this context, we propose to investigate the putative effects of Usutu virus (USUV) during mice development. USUV is a neglected arbovirus with emerging potential, for which there are no treatments or vaccines, and its biology is barely known. Our strategy aims to identify and characterize any impacts that USUV infection may cause in embryonic/fetal development using model animals for infection, namely immunodeficient and wild-type mice. We will combine classical virology and histology techniques, as well as a new microtomography technique, to study the virus infection and identify tissue changes in placentas and embryo/fetal tissues. We will look for signs of congenital malformations comparable to thosecaused by ZIKV and, if pertinent, we will characterize them under morphological and functional aspects. This project will stablish the associated risk of USUV infection, improving the knowledge about the pathogenicity of flavivirus infections. Project perspectives include designing therapeutic strategies against the pathologies caused by ZIKV and USUV during pregnancy, as well as applying this generated knowledge to other related arborviral diseases. This project is based on the specialties of the researchers involved, whose experience comprises the interface between developmental biology and arboviral infections. (AU)

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