Determination of factors governing transmission of Crimean-Congo hemorrhagic fever virus from bovines to humans

"Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen causing hemorrhagic disease in humans while being asymptomatic in non-human hosts such as bovine species. Due to the expansion of its tick vectors, CCHFV is becoming more and more threatening in Europe. Human transmission could occur via tick bites but also contact with infected fluids. In that respect, CCHFV infection via contact with animal fluids is difficult to prevent as animals have no symptoms and is therefore of high risk, especially for veterinarian and workers in slaughterhouses. The DETERMINE project aims at better understanding the determinants governing transmission from bovines to humans by combining fundamental research and sampling in the field. First, different tissues, fluids and ticks will be sampled on bovines from slaughterhouses in Cameroon, where the prevalence of CCHFV in bovines is very high. All these samples will be used for detection of viral genomes, aiming to map the factors influencing circulation of the virus but also the risk for slaughterhouse workers and the most hazardous materials. We will also determine the sequence of circulating virus aiming to determine viral residues that could promote transmission to humans. Second, we will determine and characterize molecular and cellular factors that could contribute to the control of the transmission from bovine to human with a specific focus on cellular response via interferon stimulated genes (ISG) and on entry via cellular receptors. More particularly, we will identify bovine ISGs that could be either pro- and anti-viral, study their mode of action and, by comparing the role of human and bovine ISGs, determine the molecular determinants regulating response to CCHFV infection by ISGs. Regarding cellular entry, we will compare the route of entry of particles produced in ticks, bovine and human cells in different bovines or human target cells in order to determine the interplay between transmission and molecular features of particles. Having already identified entry factors in human cells, we will determine the receptors in bovine cells and finally will identify the molecular determinants controlling the usage of human vs. bovine receptors. We believe that, by discovering the fundamental cross-species, molecular and cellular determinants of CCHFV infection, DETERMINE project will help on the one hand to anticipate CCHFV emergence but also to stimulate translational research and innovation such as identification of therapeutic targets, diagnosis tools or surveillance programs and guidelines."