The cellular host factors for severe fever with thrombocytopenia syndrome virus infection

Severe fever with thrombocytopenia syndrome (SFTS) is a newly discovered life-threatening disease caused by SFTS virus (SFTSV), an emerging tick-borne bunyavirus. The severity of SFTSV infection can vary from mild to severe, and it can be fatal in certain instances. Regrettably, there are currently no effective antiviral medications or vaccines available for treating SFTSV infection. The urgent medical needs have driven extensive research into the biology of SFTSV, with the virus-host interactions emerging as a key research focus. Similar to other viruses, SFTSV relies on host cellular factors and signaling pathways for successful replication. These host factors, which are more genetically stable than viral targets and may be shared among related viruses, are promising targets for antiviral therapy. This review highlights several important host factors, including virus entry receptors and innate immune factors. We discuss the potential SFTSV entry receptors, both the identified specific receptors and the pan-receptors utilized by multiple Bunyavirales order viruses. Other host factors essential for SFTSV entry are also summarized. After entry, SFTSV must evade the host immune system to replicate successfully, which involves regulating host cell immune pathways through interactions with immune factors. We classify and organize the natural immune host factors regulated by SFTSV according to signaling pathways. Host factors identified through functional genetics and interactome screening are also reviewed and discussed. Finally, we emphasize host factors that have been validated by targeted drugs as potential antiviral therapies for SFTSV. Our research seeks to improve the comprehension of SFTSV pathogenesis, assist in identifying effective therapeutic targets, and support the creation of antiviral medications.