The identification of host cell factors for virus entry is useful for the molecular explanation of viral tropisms and often leads to a more profound understanding of virus-induced diseases. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus. No countermeasures against the disease exist. In this report, we show an efficient method using virus-like particles for the functional screening of a cellular cDNA library to identify SFTS virus entry factors. Two variants encoding dendritic cell-specific ICAM-3 grabbing non-integrin related (DC-SIGNR), a calciumdependent lectin known to enhance SFTS virus infection, were successfully identified from a human liver cDNA library. We will discuss applications for yet unidentified factor(s) for SFTS virus entry and for entry factor(s) for other viruses related to SFTS virus.Among different organisms, many similar but non-identical cellular molecules exist that show the same functions. Even in a single species, the expressed molecules are dependent on cell types. This is the case with virus entry factors, which are cellular components involved in viral attachment to cells and invasion into cells for viral replication 1,2 . Thus, viral infections show specificity with regards to host ranges, tissues, and cell types, indicating that the identification of virus entry factors is useful for the molecular explanation of viral tropisms 3 . Because target tissues or cell types of viruses are strongly associated with virus-induced diseases, the identification of virus entry factors often leads to a more profound understanding of the associated diseases. Furthermore, the identification of viral entry factors might aid the efficient development of countermeasures against the induced diseases 4,5 .Severe fever with thrombocytopenia syndrome (SFTS) is a recently recognised tick-borne infectious disease with a high case fatality rate of up to 30%. SFTS virus, whose species name is Huaiyangshan banyangvirus (see below for details), is the causative agent 6,7 . There are no specific countermeasures against the disease. In SFTS patients, thrombocytopenia and leukopenia are frequently observed and viral antigens are often detected in the lymphoid organs in fatal cases [8][9][10][11] . In vitro, most lymphoid cell lines (e.g., Jurkat and Raji cells, which originate from T and B cells, respectively) show little susceptibility to SFTS virus infection. In contrast, most non-lymphoid cell lines (e.g., Vero cells, which originate from the kidney epithelium) show high susceptibility to the viral infection 8,12-14 . Calcium-dependent (C-type) lectins have been shown to enhance SFTS virus infection when expressed in cells that otherwise show little susceptibility 13,14 ; however, this cannot fully explain the viral tropisms because most non-lymphoid cell lines do not generally express them. Nonmuscle myosin heavy chain IIA (NMMHC-IIA) has been reported as a key entry factor of SFTS virus 15 ; however, the molecule is expressed even in Jurkat cells and ...