Multi-omics analysis of severe fever with thrombocytopenia syndrome virus infection in Rhipicephalus microplus cells reveals antiviral tick factors.

Abstract

The increasing prevalence of tick-borne arboviral infections worldwide necessitates advanced control strategies, particularly those targeting vectors, to mitigate the disease burden. However, the cellular interactions between arboviruses and ticks, especially for negative-strand RNA viruses, remain largely unexplored. Here, we employed a proteomics informed by transcriptomics approach to elucidate the cellular response of the Rhipicephalus microplus-derived BME/CTVM6 cell line to severe fever with thrombocytopenia syndrome virus (SFTSV) infection. We generated the first de novo transcriptomes and proteomes of SFTSV- and mock-infected tick cells, identifying key host responses and regulatory pathways. Additionally, interactome analysis of the viral nucleoprotein (N) integrated host responses with viral replication mechanisms. Finally, our dsRNA-mediated gene silencing screen revealed two novel anti-SFTSV effectors, the RNA helicases, DHX9 and UPF1. Collectively, our results provide new insights into the antiviral responses of Rhipicephalus microplus vector cells and highlight critical SFTSV restriction factors, while enriching transcriptomic and proteomic resources for future research.