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High Glucose Reduces Influenza and Parainfluenza Virus Productivity by Altering Glycolytic Pattern in A549 Cells
Kareem Awad1,2,3,4, Maha Abdelhadi5, Ahmed M Awad6
1Institute of Biomedicine, Faculty of Medicine, University of Turku, 20520 Turku, Finland.
Abstract:
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.
Insights
High glucose levels reduce influenza A and parainfluenza virus productivity in lung cells. This occurs with altered cell metabolism and decreased interferon-beta (IFN-β) mRNA expression, impacting viral infection outcomes.
Area of Science:
- Virology
- Cell Biology
- Metabolic Research
Background:
- Influenza A viruses cause widespread epidemics and pandemics.
- Parainfluenza viruses are significant contributors to respiratory infections and chronic lung disease.
- Understanding host-pathogen interactions under metabolic stress is crucial for public health.
Purpose of the Study:
- To investigate the impact of high glucose on influenza A and Sendai virus replication in A549 cells.
- To analyze metabolic changes, specifically glycolysis, during viral infection under hyperglycemic conditions.
- To examine the modulation of key cytokine gene expression, including interferon-beta (IFN-β) and transforming growth factor beta1 (TGF-β1), by high glucose during viral infections.
Main Methods:
- Culturing A549 immortalized cells in normal and high-glucose conditions.
- Monitoring viral productivity through virus yield quantification.
- Assessing cellular metabolism by measuring lactate release and phosphofructokinase (PFK) activity.
- Quantifying viral and cellular cytokine mRNA levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
Main Results:
- High glucose conditions significantly reduced the productivity of both influenza A and Sendai viruses.
- Increased lactate production and altered PFK activity were observed in high-glucose cultured cells during infection.
- Interferon-beta (IFN-β) mRNA expression was significantly decreased under high glucose, particularly during early infection stages.
- Influenza A H1N1 virus modulated TGF-β1 mRNA expression differently compared to Sendai virus in high glucose.
Conclusions:
- High glucose concentrations negatively impact influenza and parainfluenza virus replication in vitro.
- Metabolic alterations and suppressed IFN-β expression in high glucose may contribute to reduced viral productivity.
- These findings suggest that hyperglycemia could influence the course of viral respiratory infections and warrants consideration for personalized diagnostics and therapeutics.
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