The studies proposed for the competitive renewal period will focus on three major areas of immune response to RSV in man and in experimental animal models. These include human studies on the role of immune response in the natural history and outcome of naturally acquired RSV infection. 1) It is planned to determined the nature and possible role of immune response to major glycoproteins of RSV (especially F and G) in various immunoglobulin isotypes in serum and secretions over the course of the RSV induced bronchiolitis and wheezing. Studies will be undertaken to examine the effect of treatment with ribavirin, an antiviral chemotherapeutic agent, on the development of IgE specific antibody response to RSV glycoproteins and on the outcome of RSV associated wheezing. The role of possible release of LTC4 and LTD4 in the pathogenesis of virus induced wheezing will also be studied. 2) Other studies are proposed to examine the mechanisms of immunopathology of RSV infection in experimentally induced pulmonary disease in BALB/c mice. If is hoped to define virus and host related determinants of lung disease in animals who had been previously immunized with parenterally administered RSV. These studies will also attempt to examine the influence of RSV infection on the uptake of other environmental antigens or dietary macromolecules available in the respiratory tract. 3) Finally, long term studies are planned to explore alternative approaches to the development of immunoprophylaxis against RSV. Studies will be carried out to determine the effectiveness of intestinal immunization with RSV or RSV glycoproteins in inducing RSV specific immunologic reactivity in the respiratory tract and in protection against respiratory reinfection challenge. It is also planned to determine if immunization with isolated glycoproteins rather than whole virus will selectively limit or prevent development or RSV specific IgE response during primary immunization and during subsequent reinfection challenge. These investigations will involve routine tissue culture, immunofluorescence, Elisa and conventional immunologic procedures currently used in our laboratory.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Immunological Sciences Study Section (IMS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Medical Br Galveston
Schools of Medicine
United States
Zip Code
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
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
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

Showing the most recent 10 out of 105 publications