High Glucose Reduces Influenza and Parainfluenza Virus Productivity by Altering Glycolytic Pattern in A549 Cells

Influenza A virus is responsible for annual epidemics and occasional pandemics leading to significant mortality and morbidity in human populations. Parainfluenza viruses also contribute to lung infections and chronic lung disease. In this study, we investigated the effect of high glucose on the productivity of influenza A and Sendai (murine parainfluenza type 1) viruses in A549 immortalized cells. A glycolytic pattern of infection was determined by monitoring the release of lactate and phosphofructokinase (PFK) activity in infected and uninfected cells. qRT-PCR was used to analyze the expression of viral and cellular cytokine mRNA levels in cultured cells. The data show that the productivity of both influenza and Sendai viruses was reduced in A549 cells cultured in high-glucose conditions. This was accompanied by increased lactate production and altered PFK activity profile. Endogenous or virus infection-induced interferon β (IFN-β) mRNA expression was significantly decreased in high glucose compared to normal glucose status during early times of infection. Unlike in Sendai virus-infected cells, H1N1 virus reversed the significant increase in transforming growth factor β1 (TGF-β1) mRNA expression due to increased glucose concentration during early infection times. In conclusion, high glucose may have a negative effect on influenza and parainfluenza productivity in vitro. This effect may be considered when evaluating personalized therapeutic/diagnostic markers in infection-accompanied hyperglycemic status.