Breaking and Entering

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Science  21 Jan 2005:
Vol. 307, Issue 5708, pp. 319
DOI: 10.1126/science.307.5708.319b

Malaria begins when an infected Anopheline mosquito injects parasites into a potential host's bloodstream while feeding. The infective stage of the malaria parasite, the sporozoite, then travels to the liver through the blood-stream, where it invades hepatocytes. One of the major sporozoite surface proteins, the circumsporozoite protein (CSP), has been studied as a potential vaccine candidate, but its physiological role for the parasite within the mammalian host is unclear. Coppi et al. observed that during the invasion process, when the parasites came into contact with target cells, CSP was proteolytically cleaved by a parasite-derived papain-like cysteine protease. In the presence of inhibitors of CSP processing, invasion was blocked in vitro. Furthermore, when mice were treated with a protease inhibitor specific for papain-like proteases, sporozoite infectivity was also completely inhibited. Thus, a specific proteolytic cleavage event is important in promoting the invasion process, and interfering with this process can prevent malaria infection. — SMH

J. Exp. Med. 201, 27 (2005).

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