Intracellular ISG-virus interactions determine viral infection severity and persistence

Area of Science:

• Immunology
• Virology
• Computational Biology

Background:

• Type I interferons (IFNs) activate interferon-stimulated genes (ISGs) to control viral infections intracellularly.
• The precise impact of ISG-virus interactions on infection progression and severity is not fully understood.

Purpose of the Study:

• To develop a novel viral infection model incorporating intracellular ISG-virus dynamics.
• To analyze the influence of ISG-virus kinetics on viral infection severity and persistence.

Main Methods:

• Introduction of a new viral infection model structuring infected cells by viral load and ISG expression.
• Validation of the model using patient data for pre-alpha COVID-19 and HIV.
• Simulation of ISG-virus kinetics to study infection outcomes.

Main Results:

• Increased ISG induction can prolong infection by suppressing type I IFN production and preventing cell depletion.
• Effective ISG-mediated viral suppression is critical for managing infection severity.
• Moderate viral secretion optimizes viral load production.

Conclusions:

• The developed framework provides a computationally efficient tool for studying type I interferon signaling in viral infections.
• The model can be adapted for specific diseases and extended for therapeutic target identification.