CCR2 is a Host Entry Receptor for Severe Fever with Thrombocytopenia Syndrome Virus

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Aug 2

PMID 37531422

Authors

Leike Zhang

Xuefang Peng

Qingxing Wang

Jin Li

Shouming Lv

Shuo Han

Lingyu Zhang

Heng Ding

Cong-Yi Wang

Gengfu Xiao

Xuguang Du

Ke Peng

Hao Li

Wei Liu

Affiliations

Soon will be listed here.

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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