A Novel Mechanism Underlying Antiviral Activity of an Influenza Virus M2-Specific Antibody.
Amino Acids
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Viral
/ immunology
Antiviral Agents
/ immunology
Dogs
HEK293 Cells
Hemagglutinin Glycoproteins, Influenza Virus
/ metabolism
Humans
Influenza A virus
/ drug effects
Madin Darby Canine Kidney Cells
Mutation
Protein Binding
/ drug effects
Species Specificity
Viral Matrix Proteins
/ chemistry
Virus Release
/ drug effects
HA
M2
antibody function
antiviral mechanism
budding
influenza virus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
09 12 2020
09 12 2020
Historique:
received:
24
06
2020
accepted:
08
10
2020
pubmed:
16
10
2020
medline:
17
3
2021
entrez:
15
10
2020
Statut:
epublish
Résumé
Protective immunity against influenza A viruses (IAVs) generally depends on antibodies to the major envelope glycoprotein, hemagglutinin (HA), whose antigenicity is distinctive among IAV subtypes. On the other hand, the matrix 2 (M2) protein is antigenically highly conserved and has been studied as an attractive vaccine antigen to confer cross-protective immunity against multiple subtypes of IAVs. However, antiviral mechanisms of M2-specific antibodies are not fully understood. Here, we report the molecular basis of antiviral activity of an M2-specific monoclonal antibody (MAb), rM2ss23. We first found that rM2ss23 inhibited A/Aichi/2/1968 (H3N2) (Aichi) but not A/PR/8/1934 (H1N1) (PR8) replication. rM2ss23 altered the cell surface distribution of M2, likely by cross-linking the molecules, and interfered with the colocalization of HA and M2, resulting in reduced budding of progeny viruses. However, these effects were not observed for another strain, PR8, despite the binding capacity of rM2ss23 to PR8 M2. Interestingly, HA was also involved in the resistance of PR8 to rM2ss23. We also found that two amino acid residues at positions 54 and 57 in the M2 cytoplasmic tail were critical for the insensitivity of PR8 to rM2ss2. These findings suggest that the disruption of the M2-HA colocalization on infected cells and subsequent reduction of virus budding is one of the principal mechanisms of antiviral activity of M2-specific antibodies and that anti-M2 antibody-sensitive and -resistant IAVs have different properties in the interaction between M2 and HA.
Identifiants
pubmed: 33055251
pii: JVI.01277-20
doi: 10.1128/JVI.01277-20
pmc: PMC7737731
pii:
doi:
Substances chimiques
Amino Acids
0
Antibodies, Monoclonal
0
Antibodies, Viral
0
Antiviral Agents
0
Hemagglutinin Glycoproteins, Influenza Virus
0
M2 protein, Influenza A virus
0
Viral Matrix Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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