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

Aerin Yoon; Kye Sook Yi; So Young Chang; Sung Hwan Kim; Manki Song; Jung Ah Choi; Melissa Bourgeois; M Jaber Hossain; Li-Mei Chen; Ruben O Donis; Hyori Kim; Yujean Lee; Do Been Hwang; Ji-Young Min; Shin Jae Chang; Junho Chung

doi:10.1371/journal.pone.0141312

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.

Authors

Affiliations

¹ 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.
² Biotechnology Research Institute, Celltrion Inc., Incheon, South Korea.
³ Institut Pasteur Korea, Gyeonggi-do, South Korea.
⁴ International Vaccine Institute, Seoul, South Korea.
⁵ Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, United States of America.

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).