The Journal of Experimental Medicine
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Published 3 January 2005. doi:10.1084/jem.20040989
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 1, 27-33
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BRIEF DEFINITIVE REPORT

 The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion

Alida Coppi, Consuelo Pinzon-Ortiz, Christina Hutter, and Photini Sinnis

Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010

CORRESPONDENCE Photini Sinnis: photini.sinnis{at}med.nyu.edu

The circumsporozoite protein (CSP) is the major surface protein of Plasmodium sporozoites, the infective stage of malaria. Although CSP has been extensively studied as a malaria vaccine candidate, little is known about its structure. Here, we show that CSP is proteolytically cleaved by a papain family cysteine protease of parasite origin. Our data suggest that the highly conserved region I, found just before the repeat region, contains the cleavage site. Cleavage occurs on the sporozoite surface when parasites contact target cells. Inhibitors of CSP processing inhibit cell invasion in vitro, and treatment of mice with E-64, a highly specific cysteine protease inhibitor, completely inhibits sporozoite infectivity in vivo.


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