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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

Protective and therapeutic effects of CT302 IgG1 in influenza virus-infected mice and ferrets.(A) CT302 IgG1 was administered intraperitoneally to mice at -24, +24, or +48 hr from infection with A/NYMC X-171 strain (mouse-adapted A/Brisbane/10/2007 strain) (a, c) or A/Hong kong/1/1968 (b, d), and survival rate (a, b) and body weight change (c, d) were monitored twice daily up to 14 days. (B) Ferrets were challenged with the influenza virus and treated intravenously either with 30 mg/kg CT302 IgG1 or control IgG1 after 1 day. Subsequently, viral titers in the nasal fluid and lung tissue were determined. #p<0.05 (vs. PBS) determined by log-rank (Mantel-Cox) test. *p<0.05 (vs. control) on day 5, determined by Student’s t-test. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.
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pone.0141312.g004: Protective and therapeutic effects of CT302 IgG1 in influenza virus-infected mice and ferrets.(A) CT302 IgG1 was administered intraperitoneally to mice at -24, +24, or +48 hr from infection with A/NYMC X-171 strain (mouse-adapted A/Brisbane/10/2007 strain) (a, c) or A/Hong kong/1/1968 (b, d), and survival rate (a, b) and body weight change (c, d) were monitored twice daily up to 14 days. (B) Ferrets were challenged with the influenza virus and treated intravenously either with 30 mg/kg CT302 IgG1 or control IgG1 after 1 day. Subsequently, viral titers in the nasal fluid and lung tissue were determined. #p<0.05 (vs. PBS) determined by log-rank (Mantel-Cox) test. *p<0.05 (vs. control) on day 5, determined by Student’s t-test. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.

Mentions: The preventive potential of CT302 IgG1 against influenza virus infection was tested in mice using the A/NYMC X-171 strain (mouse-adapted A/Brisbane/10/2007 strain) and A/Hong Kong/1/1968. Influenza infection in PBS-treated control mice resulted in only 20% survival after 9 days, which was consistent throughout the 14-day experiment. All mice pretreated before influenza virus infection with CT302 IgG1, at either 2 or 10 mg/kg, survived through the two-week observation period. This demonstrates that CT302 IgG1 has a potent preventative effect against infection by strain A/NYMC X-171 (p<0.05; hazard ratio, 0.08; 95% confidence interval, 0.01–0.59). To explore the therapeutic potential of CT302 IgG1, mice were first inoculated with influenza virus and then treated with CT302 IgG1. After administering 10 mg/kg CT302 IgG1 at 24 or 48 hr postinfection, mouse survival rates were 80% (p = 0.08) or 60% (p = 0.28), respectively, at 14 days postinfection. When mice were treated either 24 or 48 hr postinfection with 2 mg/kg CT302 IgG1, the survival rates were 40% (p = 0.08 and 0.06, respectively) (Fig 4A. a). In correlation with microneutralization result, CT302 IgG1 did not show any prophylactic or therapeutic efficacy in mice infected with A/Hong Kong/1/1968 (Fig 4A.b).


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)

Protective and therapeutic effects of CT302 IgG1 in influenza virus-infected mice and ferrets.(A) CT302 IgG1 was administered intraperitoneally to mice at -24, +24, or +48 hr from infection with A/NYMC X-171 strain (mouse-adapted A/Brisbane/10/2007 strain) (a, c) or A/Hong kong/1/1968 (b, d), and survival rate (a, b) and body weight change (c, d) were monitored twice daily up to 14 days. (B) Ferrets were challenged with the influenza virus and treated intravenously either with 30 mg/kg CT302 IgG1 or control IgG1 after 1 day. Subsequently, viral titers in the nasal fluid and lung tissue were determined. #p<0.05 (vs. PBS) determined by log-rank (Mantel-Cox) test. *p<0.05 (vs. control) on day 5, determined by Student’s t-test. 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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getmorefigures.php?uid=PMC4626144&req=5

pone.0141312.g004: Protective and therapeutic effects of CT302 IgG1 in influenza virus-infected mice and ferrets.(A) CT302 IgG1 was administered intraperitoneally to mice at -24, +24, or +48 hr from infection with A/NYMC X-171 strain (mouse-adapted A/Brisbane/10/2007 strain) (a, c) or A/Hong kong/1/1968 (b, d), and survival rate (a, b) and body weight change (c, d) were monitored twice daily up to 14 days. (B) Ferrets were challenged with the influenza virus and treated intravenously either with 30 mg/kg CT302 IgG1 or control IgG1 after 1 day. Subsequently, viral titers in the nasal fluid and lung tissue were determined. #p<0.05 (vs. PBS) determined by log-rank (Mantel-Cox) test. *p<0.05 (vs. control) on day 5, determined by Student’s t-test. TCID50, tissue-culture infective dose required to cause cytopathic effects on 50% of inoculated cells.
Mentions: The preventive potential of CT302 IgG1 against influenza virus infection was tested in mice using the A/NYMC X-171 strain (mouse-adapted A/Brisbane/10/2007 strain) and A/Hong Kong/1/1968. Influenza infection in PBS-treated control mice resulted in only 20% survival after 9 days, which was consistent throughout the 14-day experiment. All mice pretreated before influenza virus infection with CT302 IgG1, at either 2 or 10 mg/kg, survived through the two-week observation period. This demonstrates that CT302 IgG1 has a potent preventative effect against infection by strain A/NYMC X-171 (p<0.05; hazard ratio, 0.08; 95% confidence interval, 0.01–0.59). To explore the therapeutic potential of CT302 IgG1, mice were first inoculated with influenza virus and then treated with CT302 IgG1. After administering 10 mg/kg CT302 IgG1 at 24 or 48 hr postinfection, mouse survival rates were 80% (p = 0.08) or 60% (p = 0.28), respectively, at 14 days postinfection. When mice were treated either 24 or 48 hr postinfection with 2 mg/kg CT302 IgG1, the survival rates were 40% (p = 0.08 and 0.06, respectively) (Fig 4A. a). In correlation with microneutralization result, CT302 IgG1 did not show any prophylactic or therapeutic efficacy in mice infected with A/Hong Kong/1/1968 (Fig 4A.b).

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