Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.
Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific mono...
| Autors principals: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
National Academy of Sciences
2017
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| _version_ | 1826296324805361664 |
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| author | Wang, X Zhu, L Dang, M Hu, Z Gao, Q Yuan, S Sun, Y Zhang, B Ren, J Kotecha, A Walter, T Wang, J Fry, E Stuart, D Rao, Z |
| author_facet | Wang, X Zhu, L Dang, M Hu, Z Gao, Q Yuan, S Sun, Y Zhang, B Ren, J Kotecha, A Walter, T Wang, J Fry, E Stuart, D Rao, Z |
| author_sort | Wang, X |
| collection | OXFORD |
| description | Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention. |
| first_indexed | 2024-03-07T04:14:35Z |
| format | Journal article |
| id | oxford-uuid:c8fd2fa4-02fb-4fa9-b5a2-8041f2ca8c44 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:14:35Z |
| publishDate | 2017 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:c8fd2fa4-02fb-4fa9-b5a2-8041f2ca8c442022-03-27T06:55:52ZPotent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c8fd2fa4-02fb-4fa9-b5a2-8041f2ca8c44EnglishSymplectic Elements at OxfordNational Academy of Sciences2017Wang, XZhu, LDang, MHu, ZGao, QYuan, SSun, YZhang, BRen, JKotecha, AWalter, TWang, JFry, EStuart, DRao, ZHepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention. |
| spellingShingle | Wang, X Zhu, L Dang, M Hu, Z Gao, Q Yuan, S Sun, Y Zhang, B Ren, J Kotecha, A Walter, T Wang, J Fry, E Stuart, D Rao, Z Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
| title | Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
| title_full | Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
| title_fullStr | Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
| title_full_unstemmed | Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
| title_short | Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site. |
| title_sort | potent neutralization of hepatitis a virus reveals a receptor mimic mechanism and the receptor recognition site |
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