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

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.

A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve

“…A/Brisbane/10/2007-ma (H3N2) used in animal challenge studies is a mouse-adapted virus derived from a PR8 reassortant virus × -171 (ref. 52 ).…”

A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis

“…To define the potential mechanism of action of mAbs, we performed a fusion assay using a specifically designed cell line. In previous studies, we studied the mechanism of action in which antibodies act on a particular virus, focused upon how viruses are blocked by antibodies after endocytosis [ 35 , 36 ]. In this study, a membrane fusion inhibition assay confirmed that low-pH-induced conformational change and cell-cell fusion were inhibited by NP-19-9 and 11B6.…”

An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus

“…This mechanism has more potential to be utilized for clinical development, because the stem region has fewer mutations than the receptor binding site. Additionally, several groups, including ours, have elucidated unconventional virus neutralizing mechanisms that affect the infection steps that occur after membrane fusion[58,59].…”