Severe respiratory viral infections: T-cell functions diverging from immunity to inflammation

Respiratory viral infections such as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and influenza A virus (IAV) trigger distinct clinical outcomes defined by immunity-based viral clearance or disease associated with exaggerated and prolonged inflammation. The important role of T cells in shaping both anti-viral immunity and inflammation has revived interest in understanding the host- pathogen interactions that lead to the diverse functions of T cells in respiratory viral infections. Inborn deficiencies and acquired insufficiency in immunity can prolong infection and shift the immune response towards exacerbated inflam-mation, which results from persistent innate immune activation and bystander T-cell activation that is nonspecific to the pathogen but is often driven by cytokines. This review discusses how virus variants, exposure doses, routes of infection, host genetics, and immune history can modulate the activation and function of T cells, thus influencing clinical outcomes. Knowledge of virus-host interaction can inform strategies to prevent immune dysfunction in respiratory viral infection and help the treatment of associated diseases.