Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody

Joseph J B Cockburn, M. Erika Navarro Sanchez, Nickolas Fretes, Agathe Urvoas, Isabelle Staropoli, Carlos M. Kikuti, Lark L Schneider, Fernando Arenzana Seisdedos, Hugues Bedouelle, Felix A. Rey

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The dengue virus (DENV) complex is composed of four distinct but serologically related flaviviruses, which together cause the present-day most important emerging viral disease. Although DENV infection induces lifelong immunity against viruses of the same serotype, the antibodies raised appear to contribute to severe disease in cases of heterotypic infections. Understanding the mechanisms of DENV neutralization by antibodies is, therefore, crucial for the design of vaccines that simultaneously protect against all four viruses. Here, we report a comparative, high-resolution crystallographic analysis of an "A-strand" murine monoclonal antibody, Mab 4E11, in complex with its target domain of the envelope protein from the four DENVs. Mab 4E11 is capable of neutralizing all four serotypes, and our study reveals the determinants of this cross-reactivity. The structures also highlight the mechanism by which A-strand Mabs disrupt the architecture of the mature virion, inducing premature fusion loop exposure and concomitant particle inactivation.

Original languageEnglish (US)
Pages (from-to)303-314
Number of pages12
JournalStructure
Volume20
Issue number2
DOIs
StatePublished - Feb 8 2012

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Dengue Virus
Monoclonal Antibodies
Virus Diseases
Viruses
Flavivirus
Antibodies
Virion
Immunity
Vaccines
Infection
Serogroup

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Cockburn, J. J. B., Navarro Sanchez, M. E., Fretes, N., Urvoas, A., Staropoli, I., Kikuti, C. M., ... Rey, F. A. (2012). Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. Structure, 20(2), 303-314. https://doi.org/10.1016/j.str.2012.01.001

Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. / Cockburn, Joseph J B; Navarro Sanchez, M. Erika; Fretes, Nickolas; Urvoas, Agathe; Staropoli, Isabelle; Kikuti, Carlos M.; Schneider, Lark L; Arenzana Seisdedos, Fernando; Bedouelle, Hugues; Rey, Felix A.

In: Structure, Vol. 20, No. 2, 08.02.2012, p. 303-314.

Research output: Contribution to journalArticle

Cockburn, JJB, Navarro Sanchez, ME, Fretes, N, Urvoas, A, Staropoli, I, Kikuti, CM, Schneider, LL, Arenzana Seisdedos, F, Bedouelle, H & Rey, FA 2012, 'Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody', Structure, vol. 20, no. 2, pp. 303-314. https://doi.org/10.1016/j.str.2012.01.001
Cockburn JJB, Navarro Sanchez ME, Fretes N, Urvoas A, Staropoli I, Kikuti CM et al. Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. Structure. 2012 Feb 8;20(2):303-314. https://doi.org/10.1016/j.str.2012.01.001
Cockburn, Joseph J B ; Navarro Sanchez, M. Erika ; Fretes, Nickolas ; Urvoas, Agathe ; Staropoli, Isabelle ; Kikuti, Carlos M. ; Schneider, Lark L ; Arenzana Seisdedos, Fernando ; Bedouelle, Hugues ; Rey, Felix A. / Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. In: Structure. 2012 ; Vol. 20, No. 2. pp. 303-314.
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