Kang Qinglin, Li Gege, Wu Yan, Wang Shaoyan, Chen Zhengshan, Zai Xiaodong, Pan Xiaoyan, Wang Rong, Lu Jiansheng, Du Peng, Yang Zhixin, Chi Xiangyang, Xiao Gengfu, Xu Junjie
School of Medicine, Zhejiang University, Hangzhou 310063, China.
Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China.
Viruses. 2024 Dec 20;16(12):1951. doi: 10.3390/v16121951.
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.
胡宁病毒（JUNV）是导致严重出血热的新大陆沙粒病毒之一。人转铁蛋白受体1（hTfR1）已被确定为JUNV进入宿主细胞的主要受体。迄今为止，尚无针对JUNV的获批治疗方法。在此，我们研究了12种抗hTfR1 VHH（重链抗体重链可变域）抗体，并证实了它们与hTfR1的相互作用。其中大多数能够结合hTfR1顶端结构域，该结构域是JUNV的糖蛋白1（GP1）结合结构域。其中，18N18对人免疫缺陷病毒（HIV）载体慢病毒胡宁假病毒和重组水疱性口炎病毒（VSV）载体胡宁假病毒均表现出中和活性。我们还验证了18N18阻断了hTfR1与JUNV GP1之间的相互作用。此外，18N18可以中和另一种新大陆沙粒病毒——马丘波病毒。通过基于AlphaFold 3的18N18 - hTfR1对接模拟，我们确定18N18的结合表位位于JUNV GP1结合表位处。18N18代表了一种JUNV治疗候选药物，并提供了一种可应用于新大陆沙粒病毒的潜在方法。
