Grant: Operating Grant

Seasonal infections with the influenza virus cause more than just a few days off work. In some patients, a secondary bacterial pneumonia can occur, triggering leaking of the blood vessels in the lung and resulting in respiratory failure. In other patients, such as the elderly or in those with a poor immune system, the virus itself can cause an overwhelming pneumonia, leading to respiratory failure even in the absence of any bacterium. In both settings, patients develop leaky blood vessels in their lungs, leading to filling of the lungs with fluid and preventing gas exchange. How influenza affects the lungs' blood vessels to make them leak is not known. In this application, we propose that infection with influenza, even at a low dose, alters or primes the lung blood vessels, making them much leakier when they are subsequently exposed to bacteria. We also suggest that high titers of the virus, such as may occur in the setting of a deficient immune system, can cause blood clots to form in the lung. These blood clots then cause the lung's blood vessels to leak. Other infected cells in the lung release chemical signals called cytokines that further stimulate blood vessels to leak. Finally, we hypothesize that preventing the lung's blood vessels from leaking will improve survival from severe influenza. This research has the potential to identify new drug targets for the treatment of severe influenza, which is one of the most common infectious causes of death in Canada.