Abstract

The broad objectives of the proposed investigations are to characterize the nature of antibody and T cell mediated immune responses to infection with respiratory syncytial virus (RSV) in infancy and childhood. It is also planned to examine the effects of pre-existing RSV specific immunologic reactivity on the outcome of subsequent RSV infection in man and in experimental settings in an animal model. The specific studies proposed in the original proposal included the following. 1. Developmental characteristics of cell mediated and antibody response in infants infected with RSV. It was proposed to examine the RSV specific immune response in relation to a) degree of viral replication and antigen load, b) alterations of RSV specific immunologic reactivity relative to the nature of clinical disease, and c) nature and the role of RSV specific secretory immune response. 2. Natural history of RSV infection-immune response interaction in infancy and early childhood. Specific longitudinal studies have been designed to delineate the mechanism responsible for development of severe clinical disease with RSV in early infancy. These studies will explore a) nature of immunologic reactivity in primary vs. secondary infection with RSV, b) clinical outcome of primary vs. secondary infection with RSV, c) effects of pre-existing serum and secretory immunologic reactivity on the outcome of RSV infection in the infant.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015939-06
Application #
3126489
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1979-09-30
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital (Buffalo)
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14222

  Publications

Haeberle, Helene A; Casola, Antonella; Gatalica, Zoran et al. (2004) IkappaB kinase is a critical regulator of chemokine expression and lung inflammation in respiratory syncytial virus infection. J Virol 78:2232-41
Tian, Bing; Brasier, Allan R (2003) Identification of a nuclear factor kappa B-dependent gene network. Recent Prog Horm Res 58:95-130
Zhang, Yuhong; Jamaluddin, Mohammad; Wang, Shaofei et al. (2003) Ribavirin treatment up-regulates antiviral gene expression via the interferon-stimulated response element in respiratory syncytial virus-infected epithelial cells. J Virol 77:5933-47
Casola, Antonella; Garofalo, Roberto P; Crawford, Sue E et al. (2002) Interleukin-8 gene regulation in intestinal epithelial cells infected with rotavirus: role of viral-induced IkappaB kinase activation. Virology 298:8-19
Haeberle, Helene A; Takizawa, Ryuta; Casola, Antonella et al. (2002) Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis 186:1199-206
Welliver, Robert C; Garofalo, Roberto P; Ogra, Pearay L (2002) Beta-chemokines, but neither T helper type 1 nor T helper type 2 cytokines, correlate with severity of illness during respiratory syncytial virus infection. Pediatr Infect Dis J 21:457-61
Jartti, Tuomas; van den Hoogen, Bernadette; Garofalo, Roberto P et al. (2002) Metapneumovirus and acute wheezing in children. Lancet 360:1393-4
Tian, Bing; Zhang, Yuhong; Luxon, Bruce A et al. (2002) Identification of NF-kappaB-dependent gene networks in respiratory syncytial virus-infected cells. J Virol 76:6800-14
Haeberle, Helene A; Nesti, Frances; Dieterich, Hans-Juergen et al. (2002) Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor-kappa B activation. Am J Respir Crit Care Med 165:1433-8
Pazdrak, Konrad; Olszewska-Pazdrak, Barbara; Liu, Tianshuang et al. (2002) MAPK activation is involved in posttranscriptional regulation of RSV-induced RANTES gene expression. Am J Physiol Lung Cell Mol Physiol 283:L364-72

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