Abstract
Emerging viruses are defined as viruses gaining new territories or as known viruses that have mutated or recombined and become more pathogenic and contagious in the population. These viruses represent major public health problems as they can sometimes cause unknown and potentially serious disorders, particularly neuroinvasive diseases. This is the case, for example, with the recent emergence of two neurotropic viruses: Zika virus (ZIKV) and Usutu virus (USUV). ZIKV is responsible for epidemics mainly in French Polynesia in 2013 and Latin America in 2015-2016, where it was also responsible for neurological disorders (encephalitis, meningoencephalitis, Guillain-Barré syndrome, microcephaly, and others) in some patients. USUV has recently emerged in Europe, where it has been implicated in significant avian mortality, mainly in blackbirds, but also in neuroinvasive infections in humans (encephalitis, meningoencephalitis, and others). Despite this, the pathogenesis of these two emerging viruses remained poorly explored. The objective of this thesis was to characterize the effects of ZIKV infection on the blood-brain barrier (BBB) structure and homeostasis and to evaluate and compare the neuropathogenicity of different USUV lineages by combining in vivo and in vitro approaches. Our results first suggest a complex interaction between ZIKV and the BBB that could trigger local inflammation, leukocyte recruitment, and possible long-term cerebrovascular impairment. Secondly, regarding USUV, our data suggest that the virus can reach the brain and cause massive inflammation leading to the recruitment of immune cells, which correlates with human brain inflammatory pathologies such as encephalitis. Also, following the analysis of circulating USUV lineages, our results suggest that some USUV lineages may have a higher degree of neurovirulence, notably the Europe 2 lineage. The emergence and rapid spread of new viruses constitute a complex and constant challenge for human health. Today, many factors such as ecological changes, increased animal movements, world population density, and improved means of transport are contributing to emerging virus appearance and facilitating their transmission. For these reasons, it is necessary to study in greater detail mechanisms of viral infection (entry of the virus into cells, transmission, multiplication, and etc.) to develop appropriate antiviral treatments or specific vaccines.Key Words: Zika Virus, Usutu Virus, flavivirus, central nervous system, neurovirulence and neurotropism