A human antibody neutralizes different flaviviruses by using different mechanisms
Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs crosslink E protein dimers at extracellular pH 8.0 condition and also when further incubated at acidic endoso...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/145978 |
| _version_ | 1811684345823363072 |
|---|---|
| author | Zhang, Shuijun Loy, Thomas Ng, Thiam-Seng Lim, Xin-Ni Chew, Valerie Shyn-Yun Tan, Ter Yong Xu, Meihui Kostyuchenko, Victor A. Tukijan, Farhana Shi, Jian Fink, Katja Lok, Shee-Mei |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Zhang, Shuijun Loy, Thomas Ng, Thiam-Seng Lim, Xin-Ni Chew, Valerie Shyn-Yun Tan, Ter Yong Xu, Meihui Kostyuchenko, Victor A. Tukijan, Farhana Shi, Jian Fink, Katja Lok, Shee-Mei |
| author_sort | Zhang, Shuijun |
| collection | NTU |
| description | Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs crosslink E protein dimers at extracellular pH 8.0 condition and also when further incubated at acidic endosomal conditions (pH 8.0-6.5). We observe Fab binding to DENV (pH 8.0-5.0) prevents virus fusion, and the number of bound Fabs increase (from 120 to 180). For ZIKV, although there are already 180 copies of Fab at pH 8.0, virus structural changes at pH 5.0 are not inhibited. The immunoglobulin G (IgG):DENV structure at pH 8.0 shows both Fab arms bind to epitopes around the 2-fold vertex. On ZIKV, an additional Fab around the 5-fold vertex at pH 8.0 suggests one IgG arm would engage with an epitope, although the other may bind to other viruses, causing aggregation. For DENV2 at pH 5.0, a similar scenario would occur, suggesting DENV2:IgG complex would aggregate in the endosome. Hence, a single antibody employs different neutralization mechanisms against different flaviviruses. |
| first_indexed | 2024-10-01T04:27:10Z |
| format | Journal Article |
| id | ntu-10356/145978 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:27:10Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1459782023-02-28T16:56:09Z A human antibody neutralizes different flaviviruses by using different mechanisms Zhang, Shuijun Loy, Thomas Ng, Thiam-Seng Lim, Xin-Ni Chew, Valerie Shyn-Yun Tan, Ter Yong Xu, Meihui Kostyuchenko, Victor A. Tukijan, Farhana Shi, Jian Fink, Katja Lok, Shee-Mei School of Biological Sciences Singapore Immunology Network, A*STAR Science::Biological sciences Dengue Virus Zika Virus Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs crosslink E protein dimers at extracellular pH 8.0 condition and also when further incubated at acidic endosomal conditions (pH 8.0-6.5). We observe Fab binding to DENV (pH 8.0-5.0) prevents virus fusion, and the number of bound Fabs increase (from 120 to 180). For ZIKV, although there are already 180 copies of Fab at pH 8.0, virus structural changes at pH 5.0 are not inhibited. The immunoglobulin G (IgG):DENV structure at pH 8.0 shows both Fab arms bind to epitopes around the 2-fold vertex. On ZIKV, an additional Fab around the 5-fold vertex at pH 8.0 suggests one IgG arm would engage with an epitope, although the other may bind to other viruses, causing aggregation. For DENV2 at pH 5.0, a similar scenario would occur, suggesting DENV2:IgG complex would aggregate in the endosome. Hence, a single antibody employs different neutralization mechanisms against different flaviviruses. National Research Foundation (NRF) Published version We thank the European Virus Archive for consenting to the use of the ZIKV H/PF/2013 strain, M.S. Diamond for sending the ZIKV, E.E. Ooi for providing DENV2 PVP94/07, and J. Wang and J.S.G. Ooi for help with the fusion assay. The work is supported by Singapore National Research Foundation Investigatorship ( NRF-NRFI2015-16 ) and Singapore National Research Foundation Competitive Research Program grants ( NRF2016NRF-CRP001-063 ). T.L. received a PhD fellowship from A∗GA under the SIgN-NTU-NUS program. 2021-01-19T07:30:52Z 2021-01-19T07:30:52Z 2020 Journal Article Zhang, S., Loy, T., Ng, T.-S., Lim, X.-N., Chew, V. S.-Y., Tan, T. Y., . . . Lok, S.-M. (2020). A human antibody neutralizes different flaviviruses by using different mechanisms. Cell Reports, 31(4), 107584-. doi:10.1016/j.celrep.2020.107584 2211-1247 https://hdl.handle.net/10356/145978 10.1016/j.celrep.2020.107584 32348755 2-s2.0-85083846765 4 31 en NRF-NRFI2015-16 NRF2016NRF-CRP001-063 Cell Reports © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
| spellingShingle | Science::Biological sciences Dengue Virus Zika Virus Zhang, Shuijun Loy, Thomas Ng, Thiam-Seng Lim, Xin-Ni Chew, Valerie Shyn-Yun Tan, Ter Yong Xu, Meihui Kostyuchenko, Victor A. Tukijan, Farhana Shi, Jian Fink, Katja Lok, Shee-Mei A human antibody neutralizes different flaviviruses by using different mechanisms |
| title | A human antibody neutralizes different flaviviruses by using different mechanisms |
| title_full | A human antibody neutralizes different flaviviruses by using different mechanisms |
| title_fullStr | A human antibody neutralizes different flaviviruses by using different mechanisms |
| title_full_unstemmed | A human antibody neutralizes different flaviviruses by using different mechanisms |
| title_short | A human antibody neutralizes different flaviviruses by using different mechanisms |
| title_sort | human antibody neutralizes different flaviviruses by using different mechanisms |
| topic | Science::Biological sciences Dengue Virus Zika Virus |
| url | https://hdl.handle.net/10356/145978 |
| work_keys_str_mv | AT zhangshuijun ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT loythomas ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT ngthiamseng ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT limxinni ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT chewvalerieshynyun ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT tanteryong ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT xumeihui ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT kostyuchenkovictora ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT tukijanfarhana ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT shijian ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT finkkatja ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT loksheemei ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT zhangshuijun humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT loythomas humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT ngthiamseng humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT limxinni humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT chewvalerieshynyun humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT tanteryong humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT xumeihui humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT kostyuchenkovictora humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT tukijanfarhana humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT shijian humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT finkkatja humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT loksheemei humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms |