Identification and characterization of GLDC as host susceptibility gene to severe influenza

Glycine decarboxylase (GLDC) modulates host antiviral response upon viral infection due to the existence of GLDC ‐pyrimidine biosynthesis‐innate immunity axis. The inter‐individual differential GLDC expression derived from genetic variation may dictate the susceptibility to severe influenza. AbstractGlycine decarboxylase (GLDC) was prioritized as a candidate susceptibility gene to severe influenza in humans. The higher expression of GLDC derived from genetic variations may confer a higher risk to H7N9 and severe H1N1 infection. We sought to characterize GLDC as functional susceptibility gene that GLDC may intrinsically regulate antiviral response, thereby impacting viral replication and disease outcome. We demonstrated that GLDC inhibitor AOAA and siRNA depletion boosted IFN β‐ and IFN‐stimulated genes (ISGs) in combination with PolyI:C stimulation. GLDC inhibition and depletion significantly amplified antiviral response of type I IFNs and ISGs upon viral infection and suppressed the replication of H1N1 and H7N9 viruses. Consistently, GLDC overexpression significan tly promoted viral replication due to the attenuated antiviral responses. Moreover, GLDC inhibition in H1N1‐infected BALB/c mice recapitulated the amplified antiviral response and suppressed viral growth. AOAA provided potent protection to the infected mice from lethal infection, comparable to a s tandard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and ...
Source: EMBO Molecular Medicine - Category: Molecular Biology Authors: Tags: Research Article Source Type: research