During the past 20 years, there has been a dramatic resurgence or emergence of epidemic virus diseases affecting both humans and domestic animals. Most of these diseases are caused by arthropod-borne viruses (arboviruses) which are transmitted from insects to hosts following blood meals. These arboviruses include, among others, members of and alphavirus genus within the Flaviviridae and Togaviridae family respectively. Dengue is the most important mosquito-borne viral disease in the world. According to a recent study, up to 400 million people are infected with Dengue flavivirus (DENV) annually and more than 2.5 billion people are at risk of contracting DENV infection. While most cases are benign and self-resolving, DF can occasionally evolve into dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) that can be lethal if not properly attended. Because of the absence of vaccine or DF-specific treatment, only symptoms can be treated. Beside this threat, Chikungunyaalphavirus is kept under surveillance due to the fact that, since 2005, it has increased its geographical area following the extension of its new vector Aedesalbopictus. These past years, CHIKV spread for the first time in the Caribbean and in American continent. There is no licensed alphavirus vaccine for human use and no specific treatment against any alphaviruses. Despite the high public health threat caused by these viruses, many questions about the tropism and pathogenesis at the cellular and molecular level remain unanswered. By studying both infections in mammals and insects, in vitro and in vivo, our global project wants to unveil the viral and/or host factors responsible for pathogenicity or resistance to infection. Using different model alphaviruses and Dengue virus, we want to explore: i) the host factors involved in entry, interspecies transmission and host susceptibility; and ii) the role of cell response in virus replication andthe spreading of viruses in vivo in mosquitoes. These understanding will help to develop new strategies to fight these public health and veterinary threats.