Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV
Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV), which has high mortality rates and poses a significant threat to public health. To identify potential therapeutic targets against SFTSV, we conduct genome-wide knockout scr...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59305-0 |
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| author | Chen Xing Cong Zhang Zhihao Xu Yajie Wang Wanqing Lu Xiaohan Liu Yingying Zhang Jingyuan Ma Shuqi Yang Yinan Du Gang Xu Yan Liu |
| author_facet | Chen Xing Cong Zhang Zhihao Xu Yajie Wang Wanqing Lu Xiaohan Liu Yingying Zhang Jingyuan Ma Shuqi Yang Yinan Du Gang Xu Yan Liu |
| author_sort | Chen Xing |
| collection | DOAJ |
| description | Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV), which has high mortality rates and poses a significant threat to public health. To identify potential therapeutic targets against SFTSV, we conduct genome-wide knockout screening, which identifies the previously known host factor CCR2, and reveals prolow-density lipoprotein receptor-related protein 1 (LRP1) as an entry factor for SFTSV. Knockdown or knockout of LRP1 significantly attenuate SFTSV infection in mouse embryonic fibroblasts (MEFs). Additionally, inhibition of LRP1 suppresses SFTSV pseudovirus infection in MEFs, suggesting its role in viral entry. The interaction between the SFTSV glycoprotein Gn and LRP1 via the CLI and CLII domains is revealed by co-IP and surface plasmon resonance (SPR). Moreover, LRP1 antagonists and neutralizing antibodies effectively attenuate SFTSV infection in MEFs. Administration of an LRP1-neutralizing antibody in a lethal male mouse model reduces the viral load, mitigates tissue damage, and improves survival. This study identifies LRP1 as a host entry receptor for SFTSV, providing a target for therapeutic strategy development. |
| format | Article |
| id | doaj-art-1d39bf2555774ffd9078abbb818f2885 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1d39bf2555774ffd9078abbb818f28852025-08-20T02:10:50ZengNature PortfolioNature Communications2041-17232025-04-0116111310.1038/s41467-025-59305-0Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSVChen Xing0Cong Zhang1Zhihao Xu2Yajie Wang3Wanqing Lu4Xiaohan Liu5Yingying Zhang6Jingyuan Ma7Shuqi Yang8Yinan Du9Gang Xu10Yan Liu11Department of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityThe First Clinical Medical School, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Anhui Medical UniversityAbstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV), which has high mortality rates and poses a significant threat to public health. To identify potential therapeutic targets against SFTSV, we conduct genome-wide knockout screening, which identifies the previously known host factor CCR2, and reveals prolow-density lipoprotein receptor-related protein 1 (LRP1) as an entry factor for SFTSV. Knockdown or knockout of LRP1 significantly attenuate SFTSV infection in mouse embryonic fibroblasts (MEFs). Additionally, inhibition of LRP1 suppresses SFTSV pseudovirus infection in MEFs, suggesting its role in viral entry. The interaction between the SFTSV glycoprotein Gn and LRP1 via the CLI and CLII domains is revealed by co-IP and surface plasmon resonance (SPR). Moreover, LRP1 antagonists and neutralizing antibodies effectively attenuate SFTSV infection in MEFs. Administration of an LRP1-neutralizing antibody in a lethal male mouse model reduces the viral load, mitigates tissue damage, and improves survival. This study identifies LRP1 as a host entry receptor for SFTSV, providing a target for therapeutic strategy development.https://doi.org/10.1038/s41467-025-59305-0 |
| spellingShingle | Chen Xing Cong Zhang Zhihao Xu Yajie Wang Wanqing Lu Xiaohan Liu Yingying Zhang Jingyuan Ma Shuqi Yang Yinan Du Gang Xu Yan Liu Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV Nature Communications |
| title | Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV |
| title_full | Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV |
| title_fullStr | Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV |
| title_full_unstemmed | Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV |
| title_short | Genome-wide CRISPR screening identifies LRP1 as an entry factor for SFTSV |
| title_sort | genome wide crispr screening identifies lrp1 as an entry factor for sftsv |
| url | https://doi.org/10.1038/s41467-025-59305-0 |
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