Cryptosporidium parvum is and enteric protozoa which primarily infects the gastrointestinal tract. Infection in the immunodeficient host, particularly with AIDS, can lead to chronic life-threatening diarrhea and wasting against which there is no effective treatment. The purpose of this continuing NCDDG program is, i) to identify and characterize selected surface molecules involved in the initial attachment of the parasite to the host cell receptor (Project 1), ii) examine the subcellular and molecular events that occur in C. parvum infected host cells relevant to drug therapy (Project 2), and iii) test the ability of specific IgA antibodies to provide immune protection against infection. Project 1 will, a) characterize the biochemical and molecular structure of Gal/GalNAc-specific C.parvum lectin, and examine its interaction with host glycoconjugates, and b) characterize the 4G12 antigen, a high molecular glycoprotein, which appears to play a role in parasite attachment to the host cell. These studies will be performed at the New England Medical Center Hospitals (NEMCH. Project 2 will, a) investigate the molecular trafficking between the parasite and the host cytoplasm through the feeder organelle, b) identify the cytoskeletal elements that form the electron dense bands and their regulation by the parasite, c) investigate the impact of infection on cell membrane surface receptors, and whether infected Caco-2 cells can be genetically altered to prolong survival and completion of parasite maturation, and d) confirm observations that the oocyst shell has, in addition delivery and targeting functions. These studies will be performed at Tufts University School of Veterinary Medicine (TUSVM). Project 2 will, a) continue the production and characterization of IgA monoclonal antibodies, using antigens and surface components previously identified by others, including the GP900 and the putative specific lectin Gal/GalNAc, b) define the capacities of IgA cloned produced to prevent or reverse infection, and c) investigate possible sites and mechanisms of IgA protection at epithelial surfaces. These studies will be performed at the Children's Hospital (CH), Harvard Medical School. The Core will provide administrative and scientific leadership and coordination for the entire program. The Core will be responsible for producing and producing and providing oocysts to the entire program, and perform all the in vivo and some of the in vitro studies required by the program. These tasks will be performed at TUSVM.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (SRC (74))
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Tufts University
Veterinary Sciences
Schools of Veterinary Medicine
United States
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Widmer, G; Akiyoshi, D; Buckholt, M A et al. (2000) Animal propagation and genomic survey of a genotype 1 isolate of Cryptosporidium parvum. Mol Biochem Parasitol 108:187-97
Cevallos, A M; Zhang, X; Waldor, M K et al. (2000) Molecular cloning and expression of a gene encoding Cryptosporidium parvum glycoproteins gp40 and gp15. Infect Immun 68:4108-16