Obesity Risk Factors Promote Metabolic Reprogramming and Viral Infection in Airways with Type 1 High Inflammation.

Area of Science:

• Immunology
• Metabolism
• Virology

Background:

• Obesity is linked to severe respiratory viral infections, particularly in asthma patients with type 1 (e.g., interferon-gamma [IFN-γ]) high inflammation.
• The interplay between obesity, saturated fatty acids (e.g., palmitic acid [PA]), and IFN-γ in airway viral infections remains unclear.

Purpose of the Study:

• To investigate the role of high-fat diet (HFD) and PA in rhinovirus infection under IFN-γ stimulation.
• To explore the therapeutic potential of a glycolytic inhibitor in models of obesity-related viral infection.

Main Methods:

• Mice models fed HFD were infected with rhinovirus and stimulated with IFN-γ.
• Primary human tracheobronchial epithelial cells were treated with PA, IFN-γ, and rhinovirus.
• The effect of 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor, was assessed.

Main Results:

• HFD and IFN-γ synergistically increased lung rhinovirus levels and neutrophilic inflammation in mice.
• PA and IFN-γ combination elevated viral load in both mouse models and human airway cells.
• Upregulation of glycolysis by HFD/PA and IFN-γ promoted viral replication; 2-DG treatment reduced viral infection.

Conclusions:

• Obesity combined with type 1 high inflammation increases susceptibility to severe respiratory viral infections.
• Targeting the glycolytic pathway or its metabolites offers a potential therapeutic strategy for managing viral infections in at-risk populations.