title: Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody.
abstract: Hepatitis E virus (HEV), a non-enveloped, positive-sense, single-stranded RNA virus, is a major cause of enteric hepatitis. Classified into the family Hepeviridae, HEV comprises four genotypes (genotypes 1-4), which belong to a single serotype. We describe a monoclonal antibody (mAb), 8G12, which equally recognizes all four genotypes of HEV, with ∼ 2.53-3.45 nM binding affinity. The mAb 8G12 has a protective, neutralizing capacity, which can significantly block virus infection in host cells. Animal studies with genotypes 1, 3 and 4 confirmed the cross-genotype neutralizing capacity of 8G12 and its effective prevention of hepatitis E disease. The complex crystal structures of 8G12 with the HEV E2s domain (the most protruded region of the virus capsid) of the abundant genotypes 1 and 4 were determined at 4.0 and 2.3 Å resolution, respectively. These structures revealed that 8G12 recognizes both genotypes through the epitopes in the E2s dimerization region. Structure-based mutagenesis and cell-model assays with virus-like particles identified several conserved residues (Glu549, Lys554 and Gly591) that are essential for 8G12 neutralization. Moreover, the epitope of 8G12 is identified as a key epitope involved in virus-host interactions. These findings will help develop a common strategy for the prevention of the most abundant form of HEV infection.
authors: 1] State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China [2] National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China.
authors: Ying
authors: Y
authors: Gu
authors: 1] Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore [2] Current address: Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
authors: Xuhua
authors: X
authors: Tang
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China.
authors: Xiao
authors: X
authors: Zhang
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors: Cuiling
authors: C
authors: Song
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors: Minghua
authors: M
authors: Zheng
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
authors: Kaihang
authors: K
authors: Wang
authors: National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China.
authors: Jun
authors: J
authors: Zhang
authors: 1] State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China [2] National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China.
authors: Mun-Hon
authors: MH
authors: Ng
authors: 1] Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore [2] Current address: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors: Choy-Leong
authors: CL
authors: Hew
authors: 1] State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China [2] National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China.
authors: Shaowei
authors: S
authors: Li
authors: 1] State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China [2] National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen, Fujian 361005, China.
authors: Ningshao
authors: N
authors: Xia
authors: Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors: J
authors: J
authors: Sivaraman
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use*; D015374:Biosensing Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005838:Genotype; D016751:Hepatitis E / Q000517:prevention & control / Q000821:virology; D016752:Hepatitis E virus / Q000276:immunology* / Q000472:pathogenicity; D008253:Macaca mulatta
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes