Induction of type I interferon by high-molecular poly-γ-glutamate protects B6.A2G-Mx1 mice against influenza A virus

In addition to development of vaccines and synthetic antiviral drugs, recent studies have advocated the use of natural substances that inhibit or prevent viral infections. High-molecular-weight poly-γ-glutamate (HM-γ-PGA) produced by Bacillus subtilis chungkookjang was evaluated for anti-influenza virus activity. HM-γ-PGA induced type I interferons (IFNs), which in turn stimulated expression of Myxovirus resistant 1 protein and IFN-related proteins in vitro. In the B6.A2G-Mx1 mouse model, which mimics the innate immune system of humans, treatment with HM-γ-PGA enhanced the antiviral state of mice and protected them against highly pathogenic influenza A virus. Naturally synthesized HM-γ-PGA has potent anti-influenza activity and may be a useful means for control of influenza virus.

► Replication of influenza A virus is inhibited by Myxovirus resistant (Mx) proteins.
► Type I interferons (IFNs) stimulate expression of Mx proteins.
► γ-PGA, a safe natural substance, induces secretion of IFNs.
► IFNs induced by γ-PGA stimulate expression of Mx proteins.
► Thereby, pretreated γ-PGA protects Mx1 congenic mice against influenza A virus.