Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape

被引：39

作者：

Gromowski, Gregory D. ^{[1
,2
]}

Roehrig, John T. ^{[5
]}

Diamond, Michael S. ^{[6
,7
,8
]}

Lee, J. Ching ^{[2
,3
,4
]}

Pitcher, Trevor J. ^{[1
,2
]}

Barrett, Alan D. T. ^{[1
,2
]}

机构：

[1] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Sealy Ctr Vaccine Dev, Dept Pathol, Galveston, TX 77555 USA

[2] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA

[3] Univ Texas Med Branch, Dept Biochem & Mol Biol, Sealy Ctr Vaccine Dev, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA

[4] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA

[5] Ctr Dis Control, Arboviral Dis Branch, Div Vector Borne Infect Dis, Ft Collins, CO 80521 USA

[6] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[7] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[8] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

来源：

VIROLOGY | 2010年 / 407卷 / 02期

关键词：

Dengue; Envelope protein domain 3; Neutralization; Monoclonal antibodies; VIRUS STRUCTURAL GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; PROTEIN GENE; FUNCTIONAL EPITOPE; TYPE-2; ANTIGEN; IDENTIFICATION; COMPLEX; PATIENT;

D O I：

10.1016/j.virol.2010.06.044

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Previous crystallographic studies have identified a total of 11 DENV-2 envelope protein domain III (ED3) residues (K305, F306, K307, V308, V309, K310, I312, Q325, P364, K388, and N390) that interacted, through both side- and main-chain contacts, with the Fab of a dengue virus (DENV) subcomplex-specific neutralizing monoclonal antibody (MAb) 1A1D-2 (Lok et al., 2008). Here, we used DENV-2 recombinant ED3 mutants of the MAb 1A1D-2 structural epitope residues to determine the functional epitope of this MAb. The side-chains of residues K307, K310 and I312 were determined to be functionally critical for MAb binding, and thus constitute a hot spot of binding energy for MAb 1A1D-2 on the DENV-2 ED3. Overall, these findings demonstrate that only a subset of the amino acid residue side-chains within the structural epitope of MAb 1A1D-2 define a functional epitope on the DENV-2 ED3 that is essential for MAb binding and neutralization escape. (C) 2010 Published by Elsevier Inc.

引用

页码：237 / 246

页数：10

共 39 条

[1] Diversity and junction residues as hotspots of binding energy in an antibody neutralizing the dengue virus [J].