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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

Inhibition of hemagglutination and cell fusion by CT302 IgG1.(A) Two-fold dilutions of CT302 IgG1 (over the range of 20 to 0.039 μg/ml in PBS) were added to wells harboring 8 hemagglutination units of influenza virus, and chicken red blood cells (RBCs) were added to a final concentration of 0.5%. Control A wells contained only RBCs and influenza virus, without CT302 IgG1. Control B wells contained only RBCs, without influenza virus or CT302 IgG1. (B) CHO cells expressing HA protein of A/Brisbane/10/2007 strain were incubated with CT302 IgG1 and then exposed to low-pH medium (pH 5.0) to induce membrane fusion. As controls, cells not treated with CT302 IgG1 but exposed to low pH, or cells not treated with CT302 IgG1 and not exposed to low pH, are shown. Magnification: 40×, 100×. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.
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pone.0141312.g002: Inhibition of hemagglutination and cell fusion by CT302 IgG1.(A) Two-fold dilutions of CT302 IgG1 (over the range of 20 to 0.039 μg/ml in PBS) were added to wells harboring 8 hemagglutination units of influenza virus, and chicken red blood cells (RBCs) were added to a final concentration of 0.5%. Control A wells contained only RBCs and influenza virus, without CT302 IgG1. Control B wells contained only RBCs, without influenza virus or CT302 IgG1. (B) CHO cells expressing HA protein of A/Brisbane/10/2007 strain were incubated with CT302 IgG1 and then exposed to low-pH medium (pH 5.0) to induce membrane fusion. As controls, cells not treated with CT302 IgG1 but exposed to low pH, or cells not treated with CT302 IgG1 and not exposed to low pH, are shown. Magnification: 40×, 100×. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.

Mentions: Next, we performed a hemagglutination inhibition assay to assess potential CT302 IgG1 inhibition of viral attachment to the sialic-acid receptor on the surface of target cells, and we performed a membrane-fusion assay to investigate CT302 IgG1’s potential inhibition of influenza virus HA-induced target-cell membrane fusion. The hemagglutination inhibition assay utilized chicken RBCs to test CT302 IgG1 against four influenza virus strains: A/Brisbane/10/2007, A/Sydney/5/1997, A/Philippines/2/1982, and A/Hong Kong/1968 strains. Even at the highest concentration tested (20 μg/ml), CT302 IgG1 did not show any hemagglutination-inhibitory activity against any of the influenza strains tested (Fig 2A), while a control antibody effectively inhibited hemagglutination in a parallel experiment (data not shown). In the absence of the influenza virus, CT302 IgG1 did not induce the hemagglutination of chicken or turkey RBCs (data not shown).


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)

Inhibition of hemagglutination and cell fusion by CT302 IgG1.(A) Two-fold dilutions of CT302 IgG1 (over the range of 20 to 0.039 μg/ml in PBS) were added to wells harboring 8 hemagglutination units of influenza virus, and chicken red blood cells (RBCs) were added to a final concentration of 0.5%. Control A wells contained only RBCs and influenza virus, without CT302 IgG1. Control B wells contained only RBCs, without influenza virus or CT302 IgG1. (B) CHO cells expressing HA protein of A/Brisbane/10/2007 strain were incubated with CT302 IgG1 and then exposed to low-pH medium (pH 5.0) to induce membrane fusion. As controls, cells not treated with CT302 IgG1 but exposed to low pH, or cells not treated with CT302 IgG1 and not exposed to low pH, are shown. Magnification: 40×, 100×. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0141312.g002: Inhibition of hemagglutination and cell fusion by CT302 IgG1.(A) Two-fold dilutions of CT302 IgG1 (over the range of 20 to 0.039 μg/ml in PBS) were added to wells harboring 8 hemagglutination units of influenza virus, and chicken red blood cells (RBCs) were added to a final concentration of 0.5%. Control A wells contained only RBCs and influenza virus, without CT302 IgG1. Control B wells contained only RBCs, without influenza virus or CT302 IgG1. (B) CHO cells expressing HA protein of A/Brisbane/10/2007 strain were incubated with CT302 IgG1 and then exposed to low-pH medium (pH 5.0) to induce membrane fusion. As controls, cells not treated with CT302 IgG1 but exposed to low pH, or cells not treated with CT302 IgG1 and not exposed to low pH, are shown. Magnification: 40×, 100×. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.
Mentions: Next, we performed a hemagglutination inhibition assay to assess potential CT302 IgG1 inhibition of viral attachment to the sialic-acid receptor on the surface of target cells, and we performed a membrane-fusion assay to investigate CT302 IgG1’s potential inhibition of influenza virus HA-induced target-cell membrane fusion. The hemagglutination inhibition assay utilized chicken RBCs to test CT302 IgG1 against four influenza virus strains: A/Brisbane/10/2007, A/Sydney/5/1997, A/Philippines/2/1982, and A/Hong Kong/1968 strains. Even at the highest concentration tested (20 μg/ml), CT302 IgG1 did not show any hemagglutination-inhibitory activity against any of the influenza strains tested (Fig 2A), while a control antibody effectively inhibited hemagglutination in a parallel experiment (data not shown). In the absence of the influenza virus, CT302 IgG1 did not induce the hemagglutination of chicken or turkey RBCs (data not shown).

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