DELV · DELta Virus infection in animal and human hosts

The emergence and rapid transmission of viruses pose increasing risks and challenges to modern societies, threatening public health and economic stability. A thorough understanding of basic virology is therefore critical for an informed development of preventive and control strategies. Although for more than 40 years the only known member of deltaviruses was the human Hepatitis Delta virus (HDV), it was recently discovered that HDV-like agents are present in a variety of animal vectors and reservoirs including bats, rats, snakes, birds and insects. Metagenomic data indicate that these satellite viruses possess an unrecognized host shifting capacity enabling them to cross the species barrier. As no efficient antiviral treatment is available against HDV, the emergence of novel deltaviruses poses a significant potential threat to human health. To date, animal deltaviruses have not been functionally characterized and little is known about their basic biology. The proposed project (DELV) aims to generate essential knowledge about the biology of deltaviruses, their interactions with host cells, their zoonotic potential and evolutionary fitness. Using newly generated deltavirus molecular clones coupled to unbiased proteomic and genetic approaches, DELV will identify host factors interacting with deltaviruses in their natural animal and human hosts (Aim 1). Further, it will determine and characterize host factors that are essential for deltavirus replication in the human host when they cross the species barrier (Aim 2). Finally, DELV will discover viral elements favoring deltavirus host shifting and adaptation capacities (Aim 3). DELV aims to shape novel paradigms in virology, RNA biology and host-pathogen interactions. Knowledge generated through DELV will guide the development of novel antiviral strategies and will have profound implications for understanding the ecology and evolution of these newly discovered, yet mysterious, viral elements.