Abstract

Infection with influenza A virus (IAV) predisposes the host to secondary bacterial infections. Exposure of PMNs to IAV inhibits a variety of cell activation steps. In the proposed project, the effect of IAV on the activation of trimeric and monomeric G-proteins will be studied. The effect of IAV on the normal movement of these G-proteins between PMN membranes and the non-membrane compartments will be studied. The effect of IAV on activation steps other than those directly involved in G- proteins will also be examined. Other studies will examine agents that reverse IAV-induced PMN end-stage dysfunction to determine if they can correct alterations in G-proteins and other activation processes. The goal of these studies is to determine the mechanisms by which IAV causes PMN dysfunction. These studies will also provide information for developing drugs to prevent or treat superinfection due to influenza and other viruses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020506-11
Application #
2671776
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1984-07-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
2001-08-31
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Pediatrics
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157

  Publications

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

Showing the most recent 10 out of 11 publications