Regulation of Host Innate Immunity in Influenza Virus Infection by Pirin and IRAK-M via PGK1
Author ORCID Identifier
Doctor of Philosophy (PhD)
Influenza virus is one of the leading agents causing human viral respiratory infections. It is characterized by seasonal epidemics and has the potential to start pandemics. The virus is a major cause of morbidity and mortality worldwide due to its potential to induce a severe inflammatory response. After decades of research, antiviral drugs and vaccines against influenza have been developed and are commercially available. However, economic and biological issues, such as antiviral resistance and vaccine mismatch, still pose a significant challenge in treating and preventing influenza infection. Therefore, strategies to develop drugs that target the host’s intracellular signaling pathways have been gaining traction. This study discusses the importance of regulating pro-inflammatory signaling pathways through negative regulators. Our study shows that the novel protein Pirin acts as a negative regulator of influenza-induced innate immunity by inhibiting RIG-I signaling in a PGK1-dependent manner. We reveal a new role for the glycolysis enzyme PGK1: it acts as a positive regulator for the influenza-induced host response by regulating IRF3 activation. Moreover, our data shows how PGK1 acts as a central regulator of RIG-I signaling, acting not only as an intermediary of Pirin regulation but also of IRAK-M, a known negative regulator of bacterial infection. Here, we show evidence of IRAK-M’s role as a negative regulator of influenza-induced innate immunity by regulating IRF3 activation in a PGK1-dependent manner. Taken together, these data offer insight into the negative regulation of influenza-induced innate immunity, which can hint at the translational potential of targeting Pirin to treat influenza infection.
Andrade Vallejo, Maria Jose, “Regulation of Host Innate Immunity in Influenza Virus Infection by Pirin and IRAK-M via PGK1.” Dissertation, Georgia State University, 2023.
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