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 language | English (US) |
|---|---|
| Pages (from-to) | 303-314 |
| Number of pages | 12 |
| Journal | Structure |
| Volume | 20 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 8 2012 |
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ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody
AU - Cockburn, Joseph J B
AU - Navarro Sanchez, M. Erika
AU - Fretes, Nickolas
AU - Urvoas, Agathe
AU - Staropoli, Isabelle
AU - Kikuti, Carlos M.
AU - Schneider, Lark L
AU - Arenzana Seisdedos, Fernando
AU - Bedouelle, Hugues
AU - Rey, Felix A.
PY - 2012/2/8
Y1 - 2012/2/8
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84856689479&partnerID=8YFLogxK
U2 - 10.1016/j.str.2012.01.001
DO - 10.1016/j.str.2012.01.001
M3 - Article
C2 - 22285214
AN - SCOPUS:84856689479
VL - 20
SP - 303
EP - 314
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 2
ER -