Podadera Ana, Leuthold Mila, Martín-Alonso José Manuel, Casais Rosa, Álvarez Angel Luis, Lobo-Castañón M J, Parra Francisco, Dalton Kevin Paul
Instituto Universitario de Biotecnología de Asturias, Departamento de Bioquímica y Biología Molecular, Edificio Santiago Gascón, Universidad de Oviedo, Campus El Cristo, 33006, Oviedo, Spain.
Chemistry and Biochemistry Department, University of Windsor, 401 Sunset Avenue, Windsor, ON, N9B 3P4, Canada.
Vet Res. 2025 Apr 2;56(1):74. doi: 10.1186/s13567-025-01505-z.
In 2010, rabbit hemorrhagic disease virus (RHDV) GI.2 emerged, and unlike RHDV GI.1, it caused mortality in young rabbits, while existing vaccines were not fully protective. The GI.2-specific monoclonal antibody (mAb) 2D9 has been used as a tool to discriminate between these viruses in diagnostic tests. In this study, we mapped the binding epitope for 2D9 on the GI.2 The VP60 capsid protein demonstrated the neutralizing capacity of this mAb, which was able to prevent GI.2 infections in an experimental challenge. Our results suggest that external loops (1, 4 and 5) in the P2 subdomain of VP60 contribute to the discontinuous neutralizing epitope recognized by mAb 2D9. Moreover, analysis of naturally occurring RHDV GI.2 isolates revealed key residues involved in mAb 2D9 binding that are under selective pressure. The findings described in this work provide valuable information regarding our understanding of virus neutralization and immune escape, which may help in the development of novel antiviral compounds.
2010年，兔出血症病毒（RHDV）GI.2出现，与RHDV GI.1不同，它可导致幼兔死亡，而现有的疫苗并不能提供完全的保护。GI.2特异性单克隆抗体（mAb）2D9已被用作在诊断测试中区分这些病毒的工具。在本研究中，我们绘制了2D9在GI.2上的结合表位。VP60衣壳蛋白证明了该单克隆抗体的中和能力，它能够在实验性攻毒中预防GI.2感染。我们的结果表明，VP60的P2亚结构域中的外部环（1、4和5）有助于形成被单克隆抗体2D9识别的不连续中和表位。此外，对天然存在的RHDV GI.2分离株的分析揭示了参与单克隆抗体2D9结合的关键残基，这些残基处于选择压力之下。这项工作中描述的发现为我们理解病毒中和及免疫逃逸提供了有价值的信息，这可能有助于新型抗病毒化合物的开发。
