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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2023
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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. |
format | Online Article Text |
id | pubmed-10396298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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