Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 201, Issue 1, Pages 27-33Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20040989
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Funding
- NIAID NIH HHS [5T32 AI07180, T32 AI007180, R01 AI056840, R01 AI44470, R01 AI044470] Funding Source: Medline
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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 1, 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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