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

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 (C...

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Autores principales: Zhang, Leike, Peng, Xuefang, Wang, Qingxing, Li, Jin, Lv, Shouming, Han, Shuo, Zhang, Lingyu, Ding, Heng, Wang, Cong-Yi, Xiao, Gengfu, Du, Xuguang, Peng, Ke, Li, Hao, Liu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396298/
https://www.ncbi.nlm.nih.gov/pubmed/37531422
http://dx.doi.org/10.1126/sciadv.adg6856
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author Zhang, Leike
Peng, Xuefang
Wang, Qingxing
Li, Jin
Lv, Shouming
Han, Shuo
Zhang, Lingyu
Ding, Heng
Wang, Cong-Yi
Xiao, Gengfu
Du, Xuguang
Peng, Ke
Li, Hao
Liu, Wei
author_facet Zhang, Leike
Peng, Xuefang
Wang, Qingxing
Li, Jin
Lv, Shouming
Han, Shuo
Zhang, Lingyu
Ding, Heng
Wang, Cong-Yi
Xiao, Gengfu
Du, Xuguang
Peng, Ke
Li, Hao
Liu, Wei
author_sort Zhang, Leike
collection PubMed
description 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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spelling pubmed-103962982023-08-03 CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus Zhang, Leike Peng, Xuefang Wang, Qingxing Li, Jin Lv, Shouming Han, Shuo Zhang, Lingyu Ding, Heng Wang, Cong-Yi Xiao, Gengfu Du, Xuguang Peng, Ke Li, Hao Liu, Wei Sci Adv Biomedicine and Life Sciences 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. American Association for the Advancement of Science 2023-08-02 /pmc/articles/PMC10396298/ /pubmed/37531422 http://dx.doi.org/10.1126/sciadv.adg6856 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Zhang, Leike
Peng, Xuefang
Wang, Qingxing
Li, Jin
Lv, Shouming
Han, Shuo
Zhang, Lingyu
Ding, Heng
Wang, Cong-Yi
Xiao, Gengfu
Du, Xuguang
Peng, Ke
Li, Hao
Liu, Wei
CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
title CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
title_full CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
title_fullStr CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
title_full_unstemmed CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
title_short CCR2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
title_sort ccr2 is a host entry receptor for severe fever with thrombocytopenia syndrome virus
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396298/
https://www.ncbi.nlm.nih.gov/pubmed/37531422
http://dx.doi.org/10.1126/sciadv.adg6856
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