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 dysfuction 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020506-02
Application #
3130211
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Abramson, J S; Hudnor, H R (1995) Role of the sialophorin (CD43) receptor in mediating influenza A virus-induced polymorphonuclear leukocyte dysfunction. Blood 85:1615-9
Abramson, J S; Hudnor, H R (1994) Effect of priming polymorphonuclear leukocytes with cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF] and G-CSF) on the host resistance to Streptococcus pneumoniae in chinchillas infected with influenza A virus. Blood 83:1929-34
Abramson, J S; Wagner, M P; Ralston, E P et al. (1991) The ability of polymorphonuclear leukocyte priming agents to overcome influenza A virus-induced cell dysfunction. J Leukoc Biol 50:160-6
Wheeler, J G; Winkler, L S; Seeds, M et al. (1990) Influenza A virus alters structural and biochemical functions of the neutrophil cytoskeleton. J Leukoc Biol 47:332-43
Cassidy, L F; Lyles, D S; Abramson, J S (1989) Depression of polymorphonuclear leukocyte functions by purified influenza virus hemagglutinin and sialic acid-binding lectins. J Immunol 142:4401-6
Cassidy, L F; Lyles, D S; Abramson, J S (1988) Synthesis of viral proteins in polymorphonuclear leukocytes infected with influenza A virus. J Clin Microbiol 26:1267-70
Abramson, J S (1988) The pathogenesis of bacterial infections in infants and children: the role of viruses. Perspect Biol Med 32:63-72
Abramson, J S; Mills, E L (1988) Depression of neutrophil function induced by viruses and its role in secondary microbial infections. Rev Infect Dis 10:326-41
Caldwell, S E; Cassidy, L F; Abramson, J S (1988) Alterations in cell protein phosphorylation in human neutrophils exposed to influenza A virus. A possible mechanism for depressed cellular end-stage functions. J Immunol 140:3560-7
Abramson, J S; Wheeler, J G; Parce, J W et al. (1986) Suppression of endocytosis in neutrophils by influenza A virus in vitro. J Infect Dis 154:456-63

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