Comparative Analyses of the Antiviral Activities of IgG and IgA Antibodies to Influenza A Virus M2 Protein
Kosuke Okuya,
Nao Eguchi,
Rashid Manzoor,
Reiko Yoshida,
Shinji Saito,
Tadaki Suzuki,
Michihito Sasaki,
Takeshi Saito,
Yurie Kida,
Akina Mori-Kajihara,
Hiroko Miyamoto,
Osamu Ichii,
Masahiro Kajihara,
Hideaki Higashi,
Ayato Takada
Affiliations
Kosuke Okuya
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Nao Eguchi
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Rashid Manzoor
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Reiko Yoshida
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Shinji Saito
Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan
Tadaki Suzuki
Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
Michihito Sasaki
Division of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Takeshi Saito
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Yurie Kida
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Akina Mori-Kajihara
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Hiroko Miyamoto
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Osamu Ichii
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan
Masahiro Kajihara
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Hideaki Higashi
Division of Infection and Immunity, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
Ayato Takada
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, N20 W10, Kita-ku, Sapporo 001-0020, Japan
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.
