1. Monoclonal antibody recognizing SLLTEVET epitope of M2 protein potently inhibited the replication of influenza A viruses in MDCK cells
- Author
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Tianhou Wang, Licheng Zhou, Xu-Guang Xi, Hongwei Xu, Yongjin Wang, Xiaoming Wang, Huiling Shi, Tetsuya Toyoda, Hong Yao, East China Normal University [Shangaï] (ECNU), Génotoxicologie et cycle cellulaire (GCC), Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), This work was supported by grants from Shanghai Municipal Science and Technology Commission (No. 07DZ22940) and Shanghai Municipal Wildlife Administration (No. SBHZ2006_01)., and We thank Dr. Yoshihiro Kawaoka from University of Madison-Wisconsin for providing the reverse genetics system for generating A/WSN/33 (H1N1) viruses.
- Subjects
MESH: Virus Replication ,[SDV]Life Sciences [q-bio] ,Peptide binding ,Influenza A ,MESH: Amino Acid Sequence ,Virus Replication ,medicine.disease_cause ,Biochemistry ,Epitope ,MESH: Dogs ,Epitopes ,Influenza A virus ,MESH: Animals ,Inhibition ,chemistry.chemical_classification ,0303 health sciences ,Antibodies, Monoclonal ,3. Good health ,Amino acid ,MESH: Viral Matrix Proteins/immunology ,Ectodomain ,Influenza Vaccines ,M2e8 ,MESH: Epitopes/genetics ,Antibody ,MESH: Viral Matrix Proteins/genetics ,Monoclonal antibody ,MESH: Mutation ,medicine.drug_class ,MESH: Influenza Vaccines/immunology ,Molecular Sequence Data ,Biophysics ,MESH: Antibodies, Monoclonal/immunology ,Biology ,Cell Line ,Viral Matrix Proteins ,03 medical and health sciences ,Dogs ,MESH: Epitopes/chemistry ,MESH: Viral Matrix Proteins/chemistry ,MESH: Influenza A virus/physiology ,medicine ,Animals ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,MESH: Molecular Sequence Data ,MESH: Epitopes/immunology ,030306 microbiology ,Cell Biology ,Virology ,Molecular biology ,In vitro ,MESH: Cell Line ,chemistry ,Mutation ,biology.protein - Abstract
International audience; The ectodomain of influenza A virus M2 protein (M2e) is composed of 24 amino acids and induces antibodies with inhibitory effect against a broad spectrum of influenza A subtypes in vitro and in vivo. Although relatively conserved, 21 M2e variants emerged in recent influenza A strains, most of the mutations appeared in the middle part of M2e domain. In this study, we characterized the in vitro inhibition efficacy of a monoclonal antibody (mAb) M2e8-7 recognizing the N terminus highly conserved epitope SLLTEVET (aa 2-9) which is common for both M1 and M2 proteins. Peptide binding assay showed that mAb M2e8-7 reacted strongly with M2e and 19 M2e variant peptides. The mAb M2e8-7 potently inhibited the replication of influenza A virus H1 and H3 subtypes in MDCK cells. Two important amino acids in M2e epitope, Threonine at position five and the Glutamic acid at position six, were identified to lead antibody-escaping variants. These results brought new insight in developing vaccine and therapeutic agents against influenza A virus infections.
- Published
- 2009
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