Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus.
Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus.
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DOI：
10.1099/vir.0.060939-0
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Mahapatra M
中科院分区：
文献类型：
--
作者：
Asfor AS;Upadhyaya S;Knowles NJ;King DP;Paton DJ;Mahapatra M
根据O型口蹄疫病毒(FMDV)的单抗逃逸突变研究，描述了5个中和抗原位点。然而，在豚鼠攻击研究中，一种被选为逃避所有五个mAb结合位点的突变病毒被证明与亲本病毒具有完全的交叉保护，表明mAb结合位点外的氨基酸残基有助于抗体介导的体内口蹄疫病毒的中和。比较牛抗血清中和一组O型口蹄疫病毒的能力，确定了VP2-74、VP2-191和VP3-85上的三个新的假定位点，其中氨基酸替换与血清反应性的变化相关。使用定点突变来测试这些位置的影响，以实现FMDV O1 Kaufbeuren(O1K)感染性拷贝中关键氨基酸残基的替换。恢复的病毒含有VP2-74和VP2-191的额外突变，与仅包括五个已知抗原位点突变的病毒相比，对O1K豚鼠和OBFS牛抗血清的中和具有更强的抵抗力。VP2-74和VP3-85的变化分别与定义抗原位点2和4的关键氨基酸相邻。然而，VP2-191(与VP2-72相距17？)位于三重轴上，距离先前已确定的抗原部位较远，表现出最深刻的影响。这些发现扩大了我们对口蹄疫病毒衣壳表面特征的了解，已知的病毒衣壳可引发中和抗体，并将改进我们的疫苗毒株选择和合理疫苗设计的策略。
Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.
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影响因子：
11.8
作者：
Ayelet G;Mahapatra M;Gelaye E;Egziabher BG;Rufeal T;Sahle M;Ferris NP;Wadsworth J;Hutchings GH;Knowles NJ
通讯作者：
Knowles NJ
影响因子：
3.3
作者：
Mahapatra, M.;Seki, C.;Paton, D. J.
通讯作者：
Paton, D. J.
影响因子：
3.8
作者：
Ellard, FM;Drew, J;King, AMQ
通讯作者：
King, AMQ
影响因子：
5.5
作者：
Brehm, K. E.;Kumar, N.;Haas, B.
通讯作者：
Haas, B.
影响因子：
3.8
作者：
CROWTHER, JR;FARIAS, S;SAMUEL, AR
通讯作者：
SAMUEL, AR