Fine antigenic variation within H5N1 influenza virus hemagglutinin's antigenic sites defined by yeast cell surface display

European Journal of Immunology - Tập 39 Số 12 - Trang 3498-3510 - 2009
Jian Li1, Yadi Wang, Yunfei Liang, Bing Ni, Ying Wan, Zhiyong Liao, K.C. Allen Chan, Kwok‐Yung Yuen, Xiaolan Fu, Shufeng Wang, Botao Guo, Biao Di, Ming Wang, Yuzhang Wu
1The Institute of Immunology, PLA, Third Military Medical University, Chongqing, P. R. China.

Tóm tắt

AbstractFifteen strains of mAb specific for HA of the A/Hong Kong/482/97 (H5N1) influenza virus were generated. The HA antigenic sites of the human A/Hong Kong/482/97 (H5N1) influenza virus were defined by using yeast cell surface‐displaying system and anti‐H5 HA mAb. Evolution analysis of H5 HA identified residues that exhibit diversifying selection in the antigenic sites and demonstrated surprising differences between residue variation of H5 HA and H3 HA. A conserved neutralizing epitope in the H5 HA protein recognized by mAb H5M9 was found using viruses isolated from 1997–2006. Seven single amino acid substitutions were introduced into the HA antigenic sites, respectively, and the alteration of antigenicity was assessed. The structure obtained by homology‐modeling and molecular dynamic methods showed that a subtle substitution at residue 124 propagates throughout its nearby loop (152–159). We discuss how the structural changes caused by point mutation might explain the altered antigenicity of the HA protein. The results demonstrate the existence of immunodominant positions in the H5 HA protein, alteration of these residues might improve the immunogenicity of vaccine strains.

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Tài liệu tham khảo

10.1016/S0140-6736(97)11212-0

10.1073/pnas.0511120103

10.3201/eid1404.071343

10.3201/eid1503.081190

10.1126/science.286.5446.1921

10.1038/nature01509

10.1073/pnas.1132114100

10.1038/289373a0

10.1128/JVI.78.15.8372-8381.2004

10.1002/9780813818634.ch19

10.1016/j.vaccine.2005.07.005

10.1016/S0264-410X(02)00139-1

10.1126/science.1097211

10.1016/j.virol.2005.03.010

10.3201/eid1008.040107

10.1016/j.vaccine.2007.09.039

10.1016/0092-8674(82)90135-0

10.1099/0022-1317-82-10-2475

Philpott M., 1989, Neutralizing epitopes of the H5 hemagglutinin from a virulent avian influenza virus and their relationship to pathogenicity, J. Virol., 63, 3453, 10.1128/jvi.63.8.3453-3458.1989

10.1128/JVI.01522-07

10.1016/S0076-6879(00)28410-3

Mischo A., 2003, Recombinant antigen expression on yeast surface (RAYS) for the detection of serological immune responses in cancer patients, Cancer Immun., 3, 5

10.1038/nrm1052

10.2174/138620708783744516

10.1099/0022-1317-83-10-2497

10.1126/science.1122665

10.1128/JCM.42.6.2629-2635.2004

10.1128/JCM.00777-06

10.1373/clinchem.2005.051045

10.1038/nature05264

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Thông tin xuất bản

European Journal of Immunology

Tập 39 Số 12

3498-3510

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