Abstract

Preliminary studies show that malarial circumsporozoites bind selectively to heparan sulfate proteoglycans and use these receptors to infect hepatocytes. Our working hypothesis is that the strong interaction between region II-plus peptides of the circumsporozoite protein and hepatocyte heparan sulfate proteoglycans requires a defined oligosaccharide sequence in the heparan sulfate chains. Our approach to identify this sequence involves (i) competition experiments with modified heparinoids with chemically defined alterations, and (ii) characterization of the proportion, size and disaccharide composition of heparan sulfate oligosaccharides that bind to CS protein/peptides.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI035703-01
Application #
3747591
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
New York University
Department
Type
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012

  Publications

Marshall, P; Rohlmann, A; Nussenzweig, V et al. (2000) Plasmodium sporozoites invade cells with targeted deletions in the LDL receptor related protein. Mol Biochem Parasitol 106:293-8
Frevert, U (1999) Heparan sulphate and RNA-binding motifs in the malaria circumsporozoite protein. Biochem Soc Trans 27:482-7
Nardin, E; Zavala, F; Nussenzweig, V et al. (1999) Pre-erythrocytic malaria vaccine: mechanisms of protective immunity and human vaccine trials. Parassitologia 41:397-402
Moreno, C A; Rodriguez, R; Oliveira, G A et al. (1999) Preclinical evaluation of a synthetic Plasmodium falciparum MAP malaria vaccine in Aotus monkeys and mice. Vaccine 18:89-99
Frevert, U; Galinski, M R; Hugel, F U et al. (1998) Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells. EMBO J 17:3816-26
Gantt, S M; Clavijo, P; Bai, X et al. (1997) Cell adhesion to a motif shared by the malaria circumsporozoite protein and thrombospondin is mediated by its glycosaminoglycan-binding region and not by CSVTCG. J Biol Chem 272:19205-13
Ying, P; Shakibaei, M; Patankar, M S et al. (1997) The malaria circumsporozoite protein: interaction of the conserved regions I and II-plus with heparin-like oligosaccharides in heparan sulfate. Exp Parasitol 85:168-82
Briones, M R; Tsuji, M; Nussenzweig, V (1996) The large difference in infectivity for mice of Plasmodium berghei and Plasmodium yoelii sporozoites cannot be correlated with their ability to enter into hepatocytes. Mol Biochem Parasitol 77:7-17
Shakibaei, M; Frevert, U (1996) Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans. J Exp Med 184:1699-711
Hugel, F U; Pradel, G; Frevert, U (1996) Release of malaria circumsporozoite protein into the host cell cytoplasm and interaction with ribosomes. Mol Biochem Parasitol 81:151-70

Showing the most recent 10 out of 14 publications