Investigations into simultaneous alphaviral infections and virus-host cell interactions

The project will be investigating the biology of arthritogenic alphaviruses, more specifically their interactions with each other and with the human host at the cellular level. It will be divided into two methodologically complementing, but independent project arms: 1. We will investigate consequences of cellular co-exposure by pairs of arthritogenic alphaviruses at the genetic level, in terms of virion composition and replication, and on the cell-intrinsic host response in order to understand the biology and potential outcome of coinfections. 2. We will identify and characterise alphavirus-specific and pan-alphaviral host dependency factors and restriction factors in a transcriptional regulation by pathogen-programmed Cas9 (TRPPC)-based gene activation screen for development of host- or virusdirected therapies. The output will increase our understanding of alphaviral interactions, identify areas of concern and potentially identify and advance novel preventive or therapeutic strategies. Alphavirus-induced disease is on the rise globally. Chikungunya virus, the most prevalent and most rapidly emerging arthritogenic alphavirus in the human population, is defined as one of the top 20 neglected tropical diseases by the WHO, highlighting the urgency to advance our knowledge on this pathogen and closely related virus species. Increasing geographic sympatry of mosquito vectors and the shared vector competence of mosquito species will probably facilitate co-infections of humans by individual alphaviruses with unknown consequences.