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J. Biol. Chem., Vol. 277, Issue 49, 47613-47618, December 6, 2002

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Function of Region I and II Adhesive Motifs of Plasmodium falciparum Circumsporozoite Protein in Sporozoite Motility and Infectivity^*

Rita Tewari, Roberta Spaccapelo^§, Francesco Bistoni^§, Anthony A. Holder^¶, and Andrea Crisanti

From the  Imperial College of Science, Technology and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom, the ^§ Department of Experimental Medicine, University of Perugia, 06100, Italy, and the ^¶ Division of Parasitology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom

The circumsporozoite protein of Plasmodium falciparum contains two conserved motifs (regions I and II) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. These data shed new light on the role of the CS protein in sporozoite motility and infectivity.

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