Tradeoffs in antiviral defense
Model for how antioxidant defense antagonizes antiviral defense in the airway epithelium. Increased activity of the oxidative stress responsive transcription factor NRF2 suppresses antiviral defense. NRF2 activity is calibrated differently in cells from different airway sites (nasal vs. bronchial). NRF2 is also activated when cells need to adapt to external oxidative stress (i.e. cigarette smoke exposure).
RV=rhinovirus. Graphic from: Mihaylova et al, Cell Reports, 2018
Like all cells in the body, airway epithelial cells are equipped with innate immune sensors to detect the presence of viral infections. When triggered, these sensors activate defense mechanisms that block viral replication. However, the local environment can greatly influence whether these defenses are robust or weak. Our work has shown that need to respond to other environmental conditions can dampen antiviral signaling within epithelial cells. Conditions that suppress antiviral defense include cool temperature or chemicals that cause oxidative damage, such as chemicals found in cigarette smoke or air pollution. To understand the intracellular signals responsible for these effects, we model viral infections in the laboratory using primary human airway epithelial cells. Our work focuses on identifying the molecular mechanisms underlying susceptibility to rhinovirus, the most frequent cause of the common cold and asthma attacks.
Video: Catching a Cold
Temperature-dependent defense against the common cold virus