Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes

Anja T R Jensen, Pamela Magistrado, Sarah Sharp, Louise Joergensen, Thomas Lavstsen, Antonella Chiucchiuini, Ali Salanti, Lasse S Vestergaard, John P Lusingu, Rob Hermsen, Robert Sauerwein, Jesper Christensen, Morten A Nielsen, Lars Hviid, Colin Sutherland, Trine Staalsoe, Thor G Theander

Abstract

Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.

OriginalsprogEngelsk
TidsskriftJournal of Experimental Medicine
Vol/bind199
Udgave nummer9
Sider (fra-til)1179-90
Antal sider12
ISSN0022-1007
DOI
StatusUdgivet - 3 maj 2004
Udgivet eksterntJa

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