Supplementary Table 3

Ticks are vectors of arboviruses in many parts of the world. The rising incidence and emergence of tick-borne arboviral infections across human populations indicates that further transmission control strategies including those based on vectors, will be required to reduce the burden of disease. However, arbovirus-tick interactions at the cellular level remain poorly understood in general, and particularly neglected for negative strand RNA arboviruses.
In this study we developed a proteomics informed by transcriptomics approach to characterize the cellular response of Rhipicephalus microplus-derived cell cultures to infection with tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV, Phenuiviridae). For this, we generated the first de novo transcriptomes and confirmed proteomes of infected and uninfected tick vector cells for SFTSV. Through comprehensive annotation of genes and proteins and pathway analysis, we identified core host responses and regulatory processes to SFTSV infection. Moreover, the viral nucleoprotein N interactome allowed us to integrate host responses with the analysis of cellular factors required for viral replication. The influence of specific genes on viral replication was assessed through dsRNA-mediated gene silencing, pinpointing two tick proteins, the RNA helicase DHX9 and the Up Frameshift Protein 1 (UPF1), as a critical antiviral tick protein controlling SFTSV. Collectively, our findings enrich the repository of resources available for understanding the antiviral response in Rh. microplus vector cells to SFTSV infection and pave the way for the development of novel vector control strategies.