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

PLoS One. 2015 Oct 29;10(10):e0141312. doi: 10.1371/journal.pone.0141312. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Antibody Affinity / immunology
  • Cell Line
  • Disease Models, Animal
  • Epitope Mapping / methods
  • Epitopes / chemistry
  • Epitopes / immunology
  • Ferrets
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Immunoglobulin G / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza, Human / immunology*
  • Influenza, Human / virology*
  • Male
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Neutralization Tests
  • Nucleoproteins / metabolism*
  • Orthomyxoviridae / physiology*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Protein Binding
  • Protein Conformation
  • Sequence Alignment
  • Virus Replication*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Nucleoproteins

Grants and funding

This study was supported in part by a grant from the Korea Healthcare Technology R&D Project‚ Ministry of Health & Welfare‚ Republic of Korea (Grant No.: A103001). Additional funding was provided by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2012R1A5A2A44671346).