Pediatric and adult patients who develop influenza virus infection are at increased risk of secondary local and systemic bacterial and fungal infections. Previous studies have shown that when human peripheral blood polymorphonuclear leukocytes are incubated with influenza virus there is depressed cellular oxidative and chemotactic activities. The mechanism for this virus-induced polymorphonuclear leukocyte dysfunction does not appear to be due to decreased receptor numbers or phagocytic activity of the cell. The cellular dysfunction is associated with virus-induced inhibition of fusion of lysosomal granules with phagosomes suggesting one possible mechanism by which the virus could depress cellular function. This project will further investigate the role of influenza virus induced disruption of lysosome-phagosome fusion in causing the abnormal oxidative and chemotactic activities that occur when cells are incubated with the virus. In addition, the mechanism by which influenza virus inhibits lysosome-phagosome fusion will be examined. Other studies will be done to determine which properties of the virus are responsible for depressed polymorphonuclear leukocyte function. These experiments will involve testing the effect on the cell of specific components of the virus which have been separated from the intact virus, comparing the properties of depressing and non-depressing virus preparations and searching for factors released from virus infected cells which inhibit granulocyte function. While the studies are designed to determine the mechanism(s) by which influenza virus alters polymorphonuclear leukocyte function, the virus should also serve as a useful probe in better understanding normal neutrophil function. An increased understanding of how influenza virus causes phagocytic cell dysfunction may allow the development of therapy to decrease the morbidity and mortality due to superinfections induced by this virus.
