A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses
The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-h...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/12/1951 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850037246949851136 |
|---|---|
| author | Qinglin Kang Gege Li Yan Wu Shaoyan Wang Zhengshan Chen Xiaodong Zai Xiaoyan Pan Rong Wang Jiansheng Lu Peng Du Zhixin Yang Xiangyang Chi Gengfu Xiao Junjie Xu |
| author_facet | Qinglin Kang Gege Li Yan Wu Shaoyan Wang Zhengshan Chen Xiaodong Zai Xiaoyan Pan Rong Wang Jiansheng Lu Peng Du Zhixin Yang Xiangyang Chi Gengfu Xiao Junjie Xu |
| author_sort | Qinglin Kang |
| collection | DOAJ |
| description | The Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-hTfR1 VHH (variable domain of the heavy chain of heavy-chain antibody) antibodies and confirmed their interaction with hTfR1. Most of them could bind to the hTfR1 apical domain, which is the glycoprotein 1 (GP1) binding domain of JUNV. Among them, 18N18 exhibited neutralizing activity against both the human immunodeficiency virus (HIV)-vectored lentiviral Junín pseudoviruses and the recombinant vesicular stomatitis virus (VSV)-vectored Junín pseudoviruses. We also verified that 18N18 blocked the interaction between hTfR1 and JUNV GP1. In addition, 18N18 could neutralize another New World arenavirus, the Machupo virus. Using AlphaFold 3-based simulation of 18N18–hTfR1 docking, we determined that 18N18’s binding epitope was located at the JUNV GP1 binding epitope. 18N18 represents a candidate for JUNV treatment and provides a potential approach that could be applied to New World arenaviruses. |
| format | Article |
| id | doaj-art-1818c28e90f44b58ad6df190a5e7ee2c |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-1818c28e90f44b58ad6df190a5e7ee2c2025-08-20T02:56:55ZengMDPI AGViruses1999-49152024-12-011612195110.3390/v16121951A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo VirusesQinglin Kang0Gege Li1Yan Wu2Shaoyan Wang3Zhengshan Chen4Xiaodong Zai5Xiaoyan Pan6Rong Wang7Jiansheng Lu8Peng Du9Zhixin Yang10Xiangyang Chi11Gengfu Xiao12Junjie Xu13School of Medicine, Zhejiang University, Hangzhou 310063, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, ChinaSchool of Medicine, Zhejiang University, Hangzhou 310063, ChinaThe Junín virus (JUNV) is one of the New World arenaviruses that cause severe hemorrhagic fever. Human transferrin receptor 1 (hTfR1) has been identified as the main receptor for JUNV for virus entry into host cells. To date, no treatment has been approved for JUNV. Herein, we investigated 12 anti-hTfR1 VHH (variable domain of the heavy chain of heavy-chain antibody) antibodies and confirmed their interaction with hTfR1. Most of them could bind to the hTfR1 apical domain, which is the glycoprotein 1 (GP1) binding domain of JUNV. Among them, 18N18 exhibited neutralizing activity against both the human immunodeficiency virus (HIV)-vectored lentiviral Junín pseudoviruses and the recombinant vesicular stomatitis virus (VSV)-vectored Junín pseudoviruses. We also verified that 18N18 blocked the interaction between hTfR1 and JUNV GP1. In addition, 18N18 could neutralize another New World arenavirus, the Machupo virus. Using AlphaFold 3-based simulation of 18N18–hTfR1 docking, we determined that 18N18’s binding epitope was located at the JUNV GP1 binding epitope. 18N18 represents a candidate for JUNV treatment and provides a potential approach that could be applied to New World arenaviruses.https://www.mdpi.com/1999-4915/16/12/1951Junín virusesMachupo virusesVHH antibodytransferrin receptor 1 |
| spellingShingle | Qinglin Kang Gege Li Yan Wu Shaoyan Wang Zhengshan Chen Xiaodong Zai Xiaoyan Pan Rong Wang Jiansheng Lu Peng Du Zhixin Yang Xiangyang Chi Gengfu Xiao Junjie Xu A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses Viruses Junín viruses Machupo viruses VHH antibody transferrin receptor 1 |
| title | A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses |
| title_full | A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses |
| title_fullStr | A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses |
| title_full_unstemmed | A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses |
| title_short | A hTfR1 Receptor-Specific VHH Antibody Neutralizes Pseudoviruses Expressing Glycoproteins from Junín and Machupo Viruses |
| title_sort | htfr1 receptor specific vhh antibody neutralizes pseudoviruses expressing glycoproteins from junin and machupo viruses |
| topic | Junín viruses Machupo viruses VHH antibody transferrin receptor 1 |
| url | https://www.mdpi.com/1999-4915/16/12/1951 |
| work_keys_str_mv | AT qinglinkang ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT gegeli ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT yanwu ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT shaoyanwang ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT zhengshanchen ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT xiaodongzai ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT xiaoyanpan ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT rongwang ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT jianshenglu ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT pengdu ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT zhixinyang ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT xiangyangchi ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT gengfuxiao ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT junjiexu ahtfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT qinglinkang htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT gegeli htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT yanwu htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT shaoyanwang htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT zhengshanchen htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT xiaodongzai htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT xiaoyanpan htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT rongwang htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT jianshenglu htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT pengdu htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT zhixinyang htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT xiangyangchi htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT gengfuxiao htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses AT junjiexu htfr1receptorspecificvhhantibodyneutralizespseudovirusesexpressingglycoproteinsfromjuninandmachupoviruses |