Comparative Analyses of the Antiviral Activities of IgG and IgA Antibodies to Influenza A Virus M2 Protein

Kosuke Okuya,Akina Mori-Kajihara,Ayato Takada,Yurie Kida,Michihito Sasaki,Reiko Yoshida,Rashid Manzoor,Masahiro Kajihara,Hideaki Higashi,Tadaki Suzuki,Shinji Saito,Osamu Ichii,Hiroko Miyamoto,Takeshi Saito,Nao Eguchi

doi:10.3390/v12070780

Kosuke Okuya, Akina Mori-Kajihara + Show 13 more

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https://doi.org/10.3390/v12070780

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Abstract

The influenza A virus (IAV) matrix-2 (M2) protein is an antigenically conserved viral envelope protein that plays an important role in virus budding together with another envelope protein, hemagglutinin (HA). An M2-specific mouse monoclonal IgG antibody, rM2ss23, which binds to the ectodomain of the M2 protein, has been shown to be a non-neutralizing antibody, but inhibits plaque formation of IAV strains. In this study, we generated chimeric rM2ss23 (ch-rM2ss23) IgG and IgA antibodies with the same variable region and compared their antiviral activities. Using gel chromatography, ch-rM2ss23 IgA were divided into three antibody subsets: monomeric IgA (m-IgA), dimeric IgA (d-IgA), and trimeric and tetrameric IgA (t/q-IgA). We found that t/q-IgA had a significantly higher capacity to reduce the plaque size of IAVs than IgG and m-IgA, most likely due to the decreased number of progeny virus particles produced from infected cells. Interestingly, HA-M2 colocalization was remarkably reduced on the infected cell surface in the presence of ch-rM2ss23 antibodies. These results indicate that anti-M2 polymeric IgA restricts IAV budding more efficiently than IgG and suggest a role of anti-M2 IgA in cross-protective immunity to IAVs.

Highlights

Influenza A viruses (IAVs) have two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the viral surface
After affinity purification of ch-rM2ss23 IgG and IgA from the supernatant, different forms of IgA antibodies were separated based on their molecular weights by gel filtration chromatography (GFC) (Figure 1a); fractions 1–4, 6–10, and 12–14 were pooled for tetrameric (or quadrimeric) IgA (t/q-IgA), dimeric IgA (d-IgA), and monomeric IgA (m-IgA), respectively
Previous studies have shown that neutralizing antibodies are not the only indicator for protective immunity against IAV infection and that non-neutralizing antibodies, which are generally produced upon immunization and vaccination, have important roles [30,38,39,40,41]

Summary

Introduction

Influenza A viruses (IAVs) have two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the viral surface. The matrix (M) gene of IAVs encodes two viral proteins, M1 and M2. The M1 protein is one of the most abundant structural components in IAV particles present on the inner leaflet of the viral envelope [2]. The M2 protein is a tetrameric integral membrane protein with an N-terminal extracellular domain (M2e) of 24 amino acids, a transmembrane domain of 19 amino acids, and a cytoplasmic tail of 54 amino acids [3]. The M2 protein possesses ion channel activity, which is important for virus entry [4]. Aside from the ion channel activity, the M2 protein possesses membrane scission activity, which is necessary to pinch off newly produced virus particles during the budding process [5].

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