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An Anti-Influenza Virus Antibody Inhibits Viral Infection by Reducing Nucleus Entry of Influenza Nucleoprotein.

Yoon A, Yi KS, Chang SY, Kim SH, Song M, Choi JA, Bourgeois M, Hossain MJ, Chen LM, Donis RO, Kim H, Lee Y, Hwang do B, Min JY, Chang SJ, Chung J - PLoS ONE (2015)

Bottom Line: To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported.In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody.This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.

ABSTRACT
To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported. Anti-globular-head-domain antibodies block either influenza virus receptor binding to the host cell or progeny virion release from the host cell. Anti-stem region antibodies hinder the membrane fusion process or induce antibody-dependent cytotoxicity to infected cells. In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody. This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

No MeSH data available.


Related in: MedlinePlus

Effect of CT302 IgG1 on the membrane fusion and the traffic of viral nucleoprotein to nucleus.Entry fusion (EF) assay: Virus particles were labeled with DiOC18 and R18, and were allowed to enter CT302 IgG1-, Bafilomycin A1- or control IgG1-treated cells. Fusion of viral and vacuolar membranes of cells triggered dequenching of DiOC18 (green) signal co-localized with the R18 (Red) signal. Nuclear import (EI assay): In the CT302 IgG1-, BafilomycinA1- or control IgG1-treated cells, virus particles were allowed to enter nucleus. Incoming NP proteins (green) were detected within the nucleus (blue) by the anti-NP antibody. Magnification: 20×.
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pone.0141312.g003: Effect of CT302 IgG1 on the membrane fusion and the traffic of viral nucleoprotein to nucleus.Entry fusion (EF) assay: Virus particles were labeled with DiOC18 and R18, and were allowed to enter CT302 IgG1-, Bafilomycin A1- or control IgG1-treated cells. Fusion of viral and vacuolar membranes of cells triggered dequenching of DiOC18 (green) signal co-localized with the R18 (Red) signal. Nuclear import (EI assay): In the CT302 IgG1-, BafilomycinA1- or control IgG1-treated cells, virus particles were allowed to enter nucleus. Incoming NP proteins (green) were detected within the nucleus (blue) by the anti-NP antibody. Magnification: 20×.

Mentions: In the cell-membrane fusion assay using CHO cells that overexpressed HA protein from A/Brisbane/10/2007 strain, CT302 IgG1 at a concentration of 10 μg/ml completely inhibited HA-dependent CHO-cell membrane fusion (Fig 2B). In viral entry fusion (EF) assay, CT302 IgG1 at the concentration of 12.5 mg/ml did not block fusion of viral and vacuolar membranes of cells (Fig 3), which is contradictory to the result of the cell-based membrane fusion assay in this study.


An Anti-Influenza Virus Antibody Inhibits Viral Infection by Reducing Nucleus Entry of Influenza Nucleoprotein.

Yoon A, Yi KS, Chang SY, Kim SH, Song M, Choi JA, Bourgeois M, Hossain MJ, Chen LM, Donis RO, Kim H, Lee Y, Hwang do B, Min JY, Chang SJ, Chung J - PLoS ONE (2015)

Effect of CT302 IgG1 on the membrane fusion and the traffic of viral nucleoprotein to nucleus.Entry fusion (EF) assay: Virus particles were labeled with DiOC18 and R18, and were allowed to enter CT302 IgG1-, Bafilomycin A1- or control IgG1-treated cells. Fusion of viral and vacuolar membranes of cells triggered dequenching of DiOC18 (green) signal co-localized with the R18 (Red) signal. Nuclear import (EI assay): In the CT302 IgG1-, BafilomycinA1- or control IgG1-treated cells, virus particles were allowed to enter nucleus. Incoming NP proteins (green) were detected within the nucleus (blue) by the anti-NP antibody. Magnification: 20×.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4626144&req=5

pone.0141312.g003: Effect of CT302 IgG1 on the membrane fusion and the traffic of viral nucleoprotein to nucleus.Entry fusion (EF) assay: Virus particles were labeled with DiOC18 and R18, and were allowed to enter CT302 IgG1-, Bafilomycin A1- or control IgG1-treated cells. Fusion of viral and vacuolar membranes of cells triggered dequenching of DiOC18 (green) signal co-localized with the R18 (Red) signal. Nuclear import (EI assay): In the CT302 IgG1-, BafilomycinA1- or control IgG1-treated cells, virus particles were allowed to enter nucleus. Incoming NP proteins (green) were detected within the nucleus (blue) by the anti-NP antibody. Magnification: 20×.
Mentions: In the cell-membrane fusion assay using CHO cells that overexpressed HA protein from A/Brisbane/10/2007 strain, CT302 IgG1 at a concentration of 10 μg/ml completely inhibited HA-dependent CHO-cell membrane fusion (Fig 2B). In viral entry fusion (EF) assay, CT302 IgG1 at the concentration of 12.5 mg/ml did not block fusion of viral and vacuolar membranes of cells (Fig 3), which is contradictory to the result of the cell-based membrane fusion assay in this study.

Bottom Line: To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported.In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody.This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.

ABSTRACT
To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported. Anti-globular-head-domain antibodies block either influenza virus receptor binding to the host cell or progeny virion release from the host cell. Anti-stem region antibodies hinder the membrane fusion process or induce antibody-dependent cytotoxicity to infected cells. In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody. This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

No MeSH data available.


Related in: MedlinePlus