Elucidating the molecular determinants of vector tropism of bunyaviruses

Alexandra Wilson

Tick-borne viruses (TBVs) present a substantial risk to human health and the economy. The order Bunyavirales contains several viruses of medical concern. Many tick-borne species of this order demonstrate the capability to maintain transmissibility for the entirety of the vector’s lifetime. Several factors have caused an increase in tick population abundance and geographical reach, thus increasing the risk of exposure to ticks and the viruses they transmit. Despite this, ticks and TBVs have historically been under-studied due to limitations on working with them in a laboratory setting, and so little is known about the intracellular interactions of these viruses within the vector that allow for sustained replication. Cellular RNA-binding proteins (RBP) have been demonstrated to promote or suppress virus replication in several mammalian host systems. However, to date, no RNA binding proteome (RBPome) has been established within the tick vector.

RNA interactome capture (RIC) is a comprehensive methodology for the systematic profiling of RBP activities in living cells. Here, we adapt this process to an Ixodes scapularis tick cell line (ISE6) in the presence or absence of Uukuniemi uukuvirus (UUKV). This novel work allows us to probe the interactions of viral RNA with cellular RBPs for the first time, establishing how bunyavirus infection alters the cellular RBPome in a cell line of arthropod origin. Our results identified 586 RBPs, of which 48% show differential RNA binding at a 10% false discovery rate (FDR) in the context of UUKV infection. We explore the change in the RBPome during infection, as well as examine the role of these interacting proteins during bunyavirus replication.

Ultimately, we hope that these data will elucidate the cellular and molecular determinates of ISE6 competence and allow us to gain a greater understanding of which RNA-protein interactions are crucial for virus replication in the arthropod.