2. Academic Validation
  3. CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus

CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus

  • Sci Adv. 2023 Aug 2;9(31):eadg6856. doi: 10.1126/sciadv.adg6856.
Leike Zhang 1 2,  Xuefang Peng 3,  Qingxing Wang 1,  Jin Li 4,  Shouming Lv 3,  Shuo Han 3,  Lingyu Zhang 3,  Heng Ding 3,  Cong-Yi Wang 5,  Gengfu Xiao 1,  Xuguang Du 4,  Ke Peng 1,  Hao Li 3 6,  Wei Liu 3 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
  • 2 Hubei Jiangxia Laboratory, Wuhan, Hubei 430200, China.
  • 3 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
  • 4 State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
  • 5 Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430040, China.
  • 6 School of Public Health, Wuhan University, Wuhan, Hubei 430071, China.
PMID: 37531422 DOI: 10.1126/sciadv.adg6856
Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus causing a high fatality rate of up to 30%. To date, the receptor mediating SFTSV entry remained uncharacterized, hindering the understanding of disease pathogenesis. Here, C-C motif Chemokine Receptor 2 (CCR2) was identified as a host receptor for SFTSV based on a genome-wide CRISPR-Cas9 screen. Knockout of CCR2 substantially reduced viral binding and Infection. CCR2 enhanced SFTSV binding through direct binding to SFTSV glycoprotein N (Gn), which is mediated by its N-terminal extracellular domain. Depletion of CCR2 in C57BL/6J mouse model attenuated SFTSV replication and pathogenesis. The peripheral blood primary monocytes from elderly individuals or subjects with underlying diabetes mellitus showed higher CCR2 surface expression and supported stronger binding and replication of SFTSV. Together, these data indicate that CCR2 is a host entry receptor for SFTSV Infection and a novel target for developing anti-SFTSV therapeutics.

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