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Merck

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

EMBO molecular medicine (2018-12-01)
Jie Zhou, Dong Wang, Bosco Ho-Yin Wong, Cun Li, Vincent Kwok-Man Poon, Lei Wen, Xiaoyu Zhao, Man Chun Chiu, Xiaojuan Liu, Ziwei Ye, Shuofeng Yuan, Kong-Hung Sze, Jasper Fuk-Woo Chan, Hin Chu, Kelvin Kai-Wang To, Kwok Yung Yuen
RESUMO

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.

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Anti-Influenza A Antibody, nucleoprotein, clone A1, clone A1, Chemicon®, from mouse