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Super-resolution microscopy reveals significant impact of M2e-specific monoclonal antibodies on influenza A virus filament formation at the host cell surface

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Abstract
Influenza A virions are highly pleomorphic, exhibiting either spherical or filamentous morphology. The influenza A virus strain A/Udorn/72 (H3N2) produces copious amounts of long filaments on the surface of infected cells where matrix protein 1(M1) and 2 (M2) play a key role in virus filament formation. Previously, it was shown that an anti-M2 ectodomain (M2e) antibody could inhibit A/Udorn/72 virus filament formation. However, the study of these structures is limited by their small size and complex structure. Here, we show that M2e-specific IgG1 and IgG2a mouse monoclonal antibodies can reduce influenza A/Udorn/72 virus plaque growth and infectivity in vitro. Using Immuno-staining combined with super-resolution microscopy that allows us to study structures beyond the diffraction limit, we report that M2 is localized at the base of viral filaments that emerge from the membrane of infected cells. Filament formation was inhibited by treatment of A/Udorn/72 infected cells with M2e-specific IgG2a and IgG1 monoclonal antibodies and resulted in fragmentation of pre-existing filaments. We conclude that M2e-specific IgGs can reduce filamentous influenza A virus replication in vitro and suggest that in vitro inhibition of A/Udorn/72 virus replication by M2e-specific antibodies correlates with the inhibition of filament formation on the surface of infected cells.
Keywords
M2 PROTEIN, EXTRACELLULAR DOMAIN, CYTOPLASMIC TAIL, MATRIX PROTEIN-2, ION-CHANNEL, M1 PROTEIN, MORPHOLOGY, MEMBRANE, GROWTH, ARCHITECTURE

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MLA
Kolpe, Annasaheb et al. “Super-resolution Microscopy Reveals Significant Impact of M2e-specific Monoclonal Antibodies on Influenza A Virus Filament Formation at the Host Cell Surface.” SCIENTIFIC REPORTS 9 (2019): n. pag. Print.
APA
Kolpe, A., Arista-Romero, M., Schepens, B., Pujals, S., Saelens, X., & Albertazzi, L. (2019). Super-resolution microscopy reveals significant impact of M2e-specific monoclonal antibodies on influenza A virus filament formation at the host cell surface. SCIENTIFIC REPORTS, 9.
Chicago author-date
Kolpe, Annasaheb, Maria Arista-Romero, Bert Schepens, Silvia Pujals, Xavier Saelens, and Lorenzo Albertazzi. 2019. “Super-resolution Microscopy Reveals Significant Impact of M2e-specific Monoclonal Antibodies on Influenza A Virus Filament Formation at the Host Cell Surface.” Scientific Reports 9.
Chicago author-date (all authors)
Kolpe, Annasaheb, Maria Arista-Romero, Bert Schepens, Silvia Pujals, Xavier Saelens, and Lorenzo Albertazzi. 2019. “Super-resolution Microscopy Reveals Significant Impact of M2e-specific Monoclonal Antibodies on Influenza A Virus Filament Formation at the Host Cell Surface.” Scientific Reports 9.
Vancouver
1.
Kolpe A, Arista-Romero M, Schepens B, Pujals S, Saelens X, Albertazzi L. Super-resolution microscopy reveals significant impact of M2e-specific monoclonal antibodies on influenza A virus filament formation at the host cell surface. SCIENTIFIC REPORTS. 2019;9.
IEEE
[1]
A. Kolpe, M. Arista-Romero, B. Schepens, S. Pujals, X. Saelens, and L. Albertazzi, “Super-resolution microscopy reveals significant impact of M2e-specific monoclonal antibodies on influenza A virus filament formation at the host cell surface,” SCIENTIFIC REPORTS, vol. 9, 2019.
@article{8611999,
  abstract     = {Influenza A virions are highly pleomorphic, exhibiting either spherical or filamentous morphology. The influenza A virus strain A/Udorn/72 (H3N2) produces copious amounts of long filaments on the surface of infected cells where matrix protein 1(M1) and 2 (M2) play a key role in virus filament formation. Previously, it was shown that an anti-M2 ectodomain (M2e) antibody could inhibit A/Udorn/72 virus filament formation. However, the study of these structures is limited by their small size and complex structure. Here, we show that M2e-specific IgG1 and IgG2a mouse monoclonal antibodies can reduce influenza A/Udorn/72 virus plaque growth and infectivity in vitro. Using Immuno-staining combined with super-resolution microscopy that allows us to study structures beyond the diffraction limit, we report that M2 is localized at the base of viral filaments that emerge from the membrane of infected cells. Filament formation was inhibited by treatment of A/Udorn/72 infected cells with M2e-specific IgG2a and IgG1 monoclonal antibodies and resulted in fragmentation of pre-existing filaments. We conclude that M2e-specific IgGs can reduce filamentous influenza A virus replication in vitro and suggest that in vitro inhibition of A/Udorn/72 virus replication by M2e-specific antibodies correlates with the inhibition of filament formation on the surface of infected cells.},
  articleno    = {4450},
  author       = {Kolpe, Annasaheb and Arista-Romero, Maria and Schepens, Bert and Pujals, Silvia and Saelens, Xavier and Albertazzi, Lorenzo},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {M2 PROTEIN,EXTRACELLULAR DOMAIN,CYTOPLASMIC TAIL,MATRIX PROTEIN-2,ION-CHANNEL,M1 PROTEIN,MORPHOLOGY,MEMBRANE,GROWTH,ARCHITECTURE},
  language     = {eng},
  pages        = {14},
  title        = {Super-resolution microscopy reveals significant impact of M2e-specific monoclonal antibodies on influenza A virus filament formation at the host cell surface},
  url          = {http://dx.doi.org/10.1038/s41598-019-41023-5},
  volume       = {9},
  year         = {2019},
}

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