Role of Glucose-6-phosphate Dehydrogenase in Viral Infection
Glucose-6-phosphate dehydrogenase(G6PD)is the first rate-limiting enzyme of the pentose phosphate pathway,which regulates the production of nicotinamide adenine dinucleotide phosphate(NADPH)in cells,and plays an important role in redox reactions.In addition,NADPH is necessary for biosynthesis reactions and is an essential hydrogen donor in the biosynthesis of cholesterol,fatty acids,and sex hormones.NADPH also plays an important role in maintaining intracellular redox homeostasis,converting intracellular oxidized glutathione into reduced glutathione(GSH),which is the main intracellular antioxidant.Therefore,G6PD plays an important role in maintaining intracellular redox homeostasis.Studies have shown that the decrease in G6PD activity can lead to a breakdown of the redox balance in the cells and tends to the oxidation state,which not only leads to dysregulation of cell growth and signaling,but also makes the host more susceptible to viruses.Previous studies have focused on the molecular characteristics of G6PD,anemia caused by G6PD deficiency,and the relationship between malignant tumors and G6PD.In recent years,more attentions have been paid to the importance of G6PD at the cellular level,development,and disease progression.To explore the effects of G6PD on viral life cycle,the relationship between G6PD and viral infections,including the clinical symptoms and virus-host interactions of hepatitis B virus(HBV),human papilloma virus(HPV),hepatitis E virus(HEV),influenza virus and dengue fever virus(DENV)will be reviewed,which will benefit the antiviral drugs development.Many studies had proved that patients with deficient G6PD are more susceptible to HBV infection.It has been reported that HBV infection activates the glycolytic pathway,promotes pentose phosphate pathway,and accelerates citric acid cycle to enhance nucleotide and fat biosynthesis,thereby promoting viral replication.During HPV infection,miR-206 up-regulates the expression of G6PD to facilitate viral replication.Thus,G6PD may be a new target for anti-cervical cancer therapy.It was reported that patients with G6PD deficiency are more susceptible to HEV infection,and more serious HEV infection-associated diseases are developed.However,the mechanism of why and how the deficiency of G6PD affect HEV infection is still unclear.The oxidative stress caused by G6PD deficiency provides a suitable environment for influenza virus replication.Furthermore,patients with G6PD deficiency are more susceptible to SARS-CoV-2 infection and lead to more severe clinical symptoms with a higher risk of thrombosis and hemolysis than general population.There is a correlation between DENV infection and G6PD deficiency,which increase the risk of hemolysis,however,the pathogenesis is still unknown.The deficiency of G6PD promotes HCoV 229E infection,possibly because the NF-κB signal pathway is suppressed when G6PD deficiency,which results in decreased innate antiviral immune,and increased susceptibility to HCoV 229E,finally leads to increased viral replication.Thus,the deficiency of G6PD play an important role during viruses'infection,especially the susceptibility.More studies should be performed on the relicationship between G6PD deficiency and specific viral susceptibility,and more attentions shoud be paid to G6PD deficient patients,which will benefit the treatment of viral infection and the development of antiviral drugs.
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