A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms
Summary: 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 acid...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720305337 |
| _version_ | 1818323560424275968 |
|---|---|
| author | Shuijun Zhang Thomas Loy Thiam-Seng Ng Xin-Ni Lim Shyn-Yun Valerie Chew Ter Yong Tan Meihui Xu Victor A. Kostyuchenko Farhana Tukijan Jian Shi Katja Fink Shee-Mei Lok |
| author_facet | Shuijun Zhang Thomas Loy Thiam-Seng Ng Xin-Ni Lim Shyn-Yun Valerie Chew Ter Yong Tan Meihui Xu Victor A. Kostyuchenko Farhana Tukijan Jian Shi Katja Fink Shee-Mei Lok |
| author_sort | Shuijun Zhang |
| collection | DOAJ |
| description | Summary: 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. : Zhang et al. show that a human monoclonal antibody SIgN-3C can neutralize closely related dengue and Zika virus via different mechanisms. The antibody neutralizes dengue virus by preventing virus:endosomal membrane fusion, although it aggregates Zika virus particles extracellularly. Keywords: dengue virus, zika virus, human antibody, virus neutralization, virus aggregation, membrane fusion, cryoEM structure |
| first_indexed | 2024-12-13T11:14:38Z |
| format | Article |
| id | doaj.art-ee0714ce4e3f486ebb66a65e9240e4d1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T11:14:38Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ee0714ce4e3f486ebb66a65e9240e4d12022-12-21T23:48:38ZengElsevierCell Reports2211-12472020-04-01314A Human Antibody Neutralizes Different Flaviviruses by Using Different MechanismsShuijun Zhang0Thomas Loy1Thiam-Seng Ng2Xin-Ni Lim3Shyn-Yun Valerie Chew4Ter Yong Tan5Meihui Xu6Victor A. Kostyuchenko7Farhana Tukijan8Jian Shi9Katja Fink10Shee-Mei Lok11Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138632, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, SingaporeProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, SingaporeProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, SingaporeProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, SingaporeProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138632, SingaporeProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138632, SingaporeCentre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore; CryoEM unit, Department of Biological Sciences, National University of Singapore, Singapore 117557, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138632, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore; Corresponding authorProgram in Emerging Infectious Diseases, Duke–National University of Singapore Medical School, Singapore 169857, Singapore; Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore; Corresponding authorSummary: 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. : Zhang et al. show that a human monoclonal antibody SIgN-3C can neutralize closely related dengue and Zika virus via different mechanisms. The antibody neutralizes dengue virus by preventing virus:endosomal membrane fusion, although it aggregates Zika virus particles extracellularly. Keywords: dengue virus, zika virus, human antibody, virus neutralization, virus aggregation, membrane fusion, cryoEM structurehttp://www.sciencedirect.com/science/article/pii/S2211124720305337 |
| spellingShingle | Shuijun Zhang Thomas Loy Thiam-Seng Ng Xin-Ni Lim Shyn-Yun Valerie Chew Ter Yong Tan Meihui Xu Victor A. Kostyuchenko Farhana Tukijan Jian Shi Katja Fink Shee-Mei Lok A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms Cell Reports |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720305337 |
| work_keys_str_mv | AT shuijunzhang ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT thomasloy ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT thiamsengng ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT xinnilim ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT shynyunvaleriechew ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT teryongtan ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT meihuixu ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT victorakostyuchenko ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT farhanatukijan ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT jianshi ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT katjafink ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT sheemeilok ahumanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT shuijunzhang humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT thomasloy humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT thiamsengng humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT xinnilim humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT shynyunvaleriechew humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT teryongtan humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT meihuixu humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT victorakostyuchenko humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT farhanatukijan humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT jianshi humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT katjafink humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms AT sheemeilok humanantibodyneutralizesdifferentflavivirusesbyusingdifferentmechanisms |