Monoclonal antibody recognizing SLLTEVET epitope of M2 protein potently inhibited the replication of influenza A viruses in MDCK cells.
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.
Wang
Yongjin
Y
Laboratory of Wildlife Epidemic Diseases, East China Normal University, Shanghai 200062, China.
Zhou
Licheng
L
Shi
Huiling
H
Xu
Hongwei
H
Yao
Hong
H
Xi
Xu Guang
XG
Toyoda
Tetsuya
T
Wang
Xiaoming
X
Wang
Tianhou
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D004285:Dogs; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000502:physiology*; D007252:Influenza Vaccines / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication; D000086082:Viroporin Proteins
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins