Abstract

Acute viral gastroenteritis is a major cause of morbidity and mortality under a wide range of clinical and environmental conditions. Our previous studies have documented that exogenously administered human immunoglobulins can modulate the intestinal replication of pathogenic viruses in humans and that inhibitors of intestinal proteases and viral attachment can prevent the in vitro replication of pathogenic enteric viruses. We propose to study the ability of immunoglobulins derived from food sources to prevent experimental and naturally occurring rotavirus infections in humans. Since immunoglobulins derived from food products are potentially available in large supply, such immunoglobulins might prove to be a practical means for the prevention of a wide range of enteric infections. We also plan to investigate the efficacy, pharmacokinetics and mechanisms of action of inhibitors of intestinal proteases and viral attachment for the prevention of enteric viral infections in animal model systems. The development of practical means of modulating enteric virus infections might result in a significant decrease in the morbidity and mortality associated with enteric virus infections in all age groups.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033089-06
Application #
3231459
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-12-01
Project End
1991-11-30
Budget Start
1989-04-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Srnka, C A; Tiemeyer, M; Gilbert, J H et al. (1992) Cell surface ligands for rotavirus: mouse intestinal glycolipids and synthetic carbohydrate analogs. Virology 190:794-805
Yolken, R H; Peterson, J A; Vonderfecht, S L et al. (1992) Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis. J Clin Invest 90:1984-91
Kinney, J; Mundorf, L; Gleason, C et al. (1991) Efficacy and pharmacokinetics of intravenous immune globulin administration to high-risk neonates. Am J Dis Child 145:1233-8
Wilde, J; Yolken, R; Willoughby, R et al. (1991) Improved detection of rotavirus shedding by polymerase chain reaction. Lancet 337:323-6
Yolken, R H; Maldonado, Y; Kinney, J et al. (1990) Epidemiology and potential methods for prevention of neonatal intestinal viral infections. Rev Infect Dis 12 Suppl 4:S421-7
Willoughby, R E; Yolken, R H; Schnaar, R L (1990) Rotaviruses specifically bind to the neutral glycosphingolipid asialo-GM1. J Virol 64:4830-5
Kinney, J S; Viscidi, R P; Vonderfecht, S L et al. (1989) Monoclonal antibody assay for detection of double-stranded RNA and application for detection of group A and non-group A rotaviruses. J Clin Microbiol 27:6-12
Yolken, R; Dubovi, E; Leister, F et al. (1989) Infantile gastroenteritis associated with excretion of pestivirus antigens. Lancet 1:517-20
Yolken, R; Wee, S B; Eiden, J et al. (1988) Identification of a group-reactive epitope of group B rotaviruses recognized by monoclonal antibody and application to the development of a sensitive immunoassay for viral characterization. J Clin Microbiol 26:1853-8
Willoughby, R E; Wee, S B; Yolken, R H (1988) Non-group A rotavirus infection associated with severe gastroenteritis in a bone marrow transplant patient. Pediatr Infect Dis J 7:133-5

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