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A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms.

Zhang S, Loy T, Ng TS, Lim XN, Chew SV, Tan TY, Xu M, Kostyuchenko VA, Tukijan F, Shi J, Fink K, Lok SM
Cell Rep 31 107584 (2020)
Related entries: 7bu8, 7bub, 7bud, 7bue, 7buf

Cited: 13 times
EuropePMC logo PMID: 32348755

Abstract

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.

Articles - 7bua mentioned but not cited (2)

  1. research-article The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies. Kikawa C, Cartwright-Acar CH, Stuart JB, Contreras M, Levoir LM, Evans MJ, Bloom JD, Goo L. bioRxiv 2023.09.13.557606 (2023)
  2. The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies. Kikawa C, Cartwright-Acar CH, Stuart JB, Contreras M, Levoir LM, Evans MJ, Bloom JD, Goo L. J Virol 97 e0141423 (2023)


Reviews citing this publication (6)

  1. Protective and enhancing interactions among dengue viruses 1-4 and Zika virus. Katzelnick LC, Bos S, Harris E. Curr Opin Virol 43 59-70 (2020)
  2. Recent advances in immunotherapies against infectious diseases. Ramamurthy D, Nundalall T, Cingo S, Mungra N, Karaan M, Naran K, Barth S. Immunother Adv 1 ltaa007 (2021)
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  4. How Antibodies Recognize Pathogenic Viruses: Structural Correlates of Antibody Neutralization of HIV-1, SARS-CoV-2, and Zika. Abernathy ME, Dam KA, Esswein SR, Jette CA, Bjorkman PJ. Viruses 13 2106 (2021)
  5. Development of Therapeutic Monoclonal Antibodies for Emerging Arbovirus Infections. Ormundo LF, Barreto CT, Tsuruta LR. Viruses 15 2177 (2023)
  6. Generating prophylactic immunity against arboviruses in vertebrates and invertebrates. Rawle DJ, Hugo LE, Cox AL, Devine GJ, Suhrbier A. Nat Rev Immunol 24 621-636 (2024)

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