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TitleThe structural basis for serotype-specific neutralization of dengue virus by a human antibody.
Journal, issue, pagesSci Transl Med, Vol. 4, Issue 139, Page 139ra83, Year 2012
Publish dateJun 20, 2012
AuthorsEe Ping Teoh / Petra Kukkaro / En Wei Teo / Angeline P C Lim / Tze Tong Tan / Andy Yip / Wouter Schul / Myint Aung / Victor A Kostyuchenko / Yee Sin Leo / Soh Ha Chan / Kenneth G C Smith / Annie Hoi Yi Chan / Gang Zou / Eng Eong Ooi / D Michael Kemeny / Grace K Tan / Jowin K W Ng / Mah Lee Ng / Sylvie Alonso / Dale Fisher / Pei-Yong Shi / Brendon J Hanson / Shee-Mei Lok / Paul A MacAry /
PubMed AbstractDengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to ...Dengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to that serotype but offers only transient protection against the other serotypes. Identification of the protective determinants of the human antibody response to DENV is a vital requirement for the design and evaluation of future preventative therapies and treatments. Here, we describe the isolation of a neutralizing antibody from a DENV1-infected patient. The human antibody 14c10 (HM14c10) binds specifically to DENV1. HM14c10 neutralizes the virus principally by blocking virus attachment; at higher concentrations, a post-attachment step can also be inhibited. In vivo studies show that the HM14c10 antibody has antiviral activity at picomolar concentrations. A 7 Å resolution cryoelectron microscopy map of Fab fragments of HM14c10 in a complex with DENV1 shows targeting of a discontinuous epitope that spans the adjacent surface of envelope protein dimers. As found previously, a human antibody specific for the related West Nile virus binds to a similar quaternary structure, suggesting that this could be an immunodominant epitope. These findings provide a structural and molecular context for durable, serotype-specific immunity to DENV infection.
External linksSci Transl Med / PubMed:22723463
MethodsEM (single particle)
Resolution7.0 Å
Structure data

EMDB-5268, PDB-3j05:
Three-dimensional structure of Dengue virus serotype 1 complexed with HMAb 14c10 Fab
PDB-4cau: THREE-DIMENSIONAL STRUCTURE OF DENGUE VIRUS SEROTYPE 1 COMPLEXED WITH 2 HMAB 14C10 FAB
Method: EM (single particle) / Resolution: 7.0 Å

Source
  • homo sapiens (human)
  • dengue virus 1
KeywordsVIRUS / flavivirus / dengue / serotype 1 / envelope protein / E protein / mature virus / ANTIBODIES / HUMAN ANTIBODIES / MONOCLONAL ANTIBODIES / HMAB

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