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Infection and Immunity, October 2007, p. 4838-4850, Vol. 75, No. 10
0019-9567/07/$08.00+0     doi:10.1128/IAI.00635-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Six Genes Are Preferentially Transcribed by the Circulating and Sequestered Forms of Plasmodium falciparum Parasites That Infect Pregnant Women ^,

Susan E. Francis,¹ Vladislav A. Malkov,^1, Andrew V. Oleinikov,¹ Eddie Rossnagle,¹ Jason P. Wendler,^1, Theonest K. Mutabingwa,^1,2,3 Michal Fried,^1,4 and Patrick E. Duffy^1,4*

Seattle Biomedical Research Institute, Seattle, Washington 98109,¹ National Institute for Medical Research, Dar es Salaam, Tanzania,² Muheza Designated District Hospital, Muheza, Tanzania,³ University of Washington, Seattle, Washington 98195⁴

Received 4 May 2007/ Returned for modification 17 June 2007/ Accepted 1 August 2007

In areas of stable malaria transmission, susceptibility to Plasmodium falciparum malaria increases during first pregnancy. Women become resistant to pregnancy malaria over successive pregnancies as they acquire antibodies against the parasite forms that sequester in the placenta, suggesting that a vaccine is feasible. Placental parasites are antigenically distinct and bind receptors, like chondroitin sulfate A (CSA), that are not commonly bound by other parasites. We used whole-genome-expression analysis to find transcripts that distinguish parasites of pregnant women from other parasites and employed a novel approach to define and adjust for cell cycle timing of parasites. Transcription of six genes was substantially higher in both placental parasites and peripheral parasites from pregnant women, and each gene encodes a protein with a putative export sequence and/or transmembrane domain. This cohort of genes includes var2csa, a member of the variant PfEMP1 gene family previously implicated in pregnancy malaria, as well as five conserved genes of unknown functions. Women in East Africa acquire antibodies over successive pregnancies against a protein encoded by one of these genes, PFD1140w, and this protein shows seroreactivity similar to that of VAR2CSA domains. These findings suggest that a suite of genes may be important for the genesis of the placental binding phenotype of P. falciparum and may provide novel targets for therapeutic intervention.

Published ahead of print on 13 August 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. F. Urban, Jr.

Present address: Merck & Co., Inc., Seattle, WA 98109.

Present address: University of Nebraska, Lincoln, NE.

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