Fried Michal, Hixson Kim K, Anderson Lori, Ogata Yuko, Mutabingwa Theonest K, Duffy Patrick E
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Mol Biochem Parasitol. 2007 Sep;155(1):57-65. doi: 10.1016/j.molbiopara.2007.05.010. Epub 2007 May 29.
Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.
恶性疟原虫感染的红细胞（IE）表面表达的疟疾蛋白介导黏附作用，并成为保护性免疫反应的靶点。在孕期，IE会滞留于胎盘。胎盘IE与硫酸软骨素A（CSA）分子结合，并优先转录编码VAR2CSA的基因，VAR2CSA是恶性疟原虫红细胞膜蛋白1（PfEMP1）变体表面抗原家族的成员。在连续妊娠过程中，女性会对结合CSA的IE以及VAR2CSA抗体产生特异性免疫。我们运用串联质谱技术以及精确质量与时间标签技术，研究胎盘寄生虫的IE膜组分。在胎盘IE以及儿童的IE中均检测到了VAR2CSA肽段，但VAR2CSA的MC变体与胎盘IE具有特异性关联。我们鉴定出六种带有假定跨膜（TM）或信号肽的保守假设蛋白，这些蛋白仅由胎盘IE表达，还有11种此类蛋白在胎盘IE中含量显著更高。其中一种假设蛋白PFI1785w是一种42kDa的分子，通过蛋白质印迹法在感染孕妇的寄生虫中检测到，而在感染儿童的寄生虫中未检测到。
