Glycine 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 IFNβ‐ 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 significantly 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 standard antiviral against influenza viruses. Collectively, GLDC regulates cellular antiviral response and orchestrates viral growth. GLDC is a functional susceptibility gene to severe influenza in humans.

甘氨酸脱羧酶（GLDC）被优先考虑作为人类严重流感的候选易感基因。来自遗传变异的GLDC的较高表达可能赋予H7N9和严重H1N1感染更高的风险。我们试图将GLDC表征为功能敏感基因，GLDC可能在本质上调节抗病毒反应，从而影响病毒复制和疾病结局。我们表明，GLDC抑制剂AOAA和Si RNA耗尽升压IFN β-和IFN刺激的基因（ISG多个）结合聚I：C的刺激。GLDC抑制和耗竭显着增强了病毒感染后I型IFN和ISG的抗病毒反应，并抑制了H1N1和H7N9病毒的复制。一致地，由于抗病毒反应减弱，GLDC的过表达显着促进了病毒复制。此外，在H1N1感染的BALB / c小鼠中，GLDC抑制作用概括了放大的抗病毒反应并抑制了病毒的生长。AOAA为感染的小鼠提供了有效的保护，使其免受致死性感染，相当于标准的抗流感病毒抗病毒药。总的来说，GLDC调节细胞的抗病毒反应并协调病毒的生长。GLDC 是人类严重流感的功能易感基因。