CHEMICAL & ENGINEERING
NEWS OF THE WEEK JUNE 27, 2005 - EDITED BY JANET S. DODD & MELISSA BRADDOCK
MOLECULAR
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BIOLOGY
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MALARIA DEFENSE MECHANISM BARED
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Hemoglobin C reduces display of malaria parasite protein on host cells
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VARIANT FORM OF HEMO-
globin may protect against malaria by preventing the malaria parasite from expressing a protein on the surface of host red blood cells. Scientists have known for five years that West Africans with the variant hemoglobin C are pro tected against severe malaria. Pre vious studies have shown that hemoglobin C reduces the preval ence of severe malaria by as much as 80%, but the mechanism ofthat protection has been a mystery Now, Thomas E. Wellems, chief of the Laboratory ofMalar ia & Vector Research at NIH in Bethesda, Md., and his interna tional team of researchers think they have the answer.
fected cells to adhere to en dothelial cells that line the tiny bloodvessels of the host circula tory system, where the parasites can sequester themselves. In addition, PfEMP-1 allows in fected host cells to stick to unin fected red blood cells in a pro cess called rosetting, producing clumps that can impair blood flow in critical tissues such as the brain. The researchers find that infect ed red blood cells containing he moglobin C are less able to adhere to endothelial cells and other red blood cells in malaria {Nature 2005,435,1117). Hemoglobin C is less stable than normal hemoglobin A, which may explain its effects. Oxidation ofhemoglobin C appears to affect
Endemic malaria
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1 Malaria marginal/ epidemic prone
ways to reduce the impact of malaria," Wellems says. PfEMP-1 will be a tough target for drugs or vaccines, however, attacking this tar get with a vaccine is going to be very difficult because it's an antigenically variable molecule" that can be encoded by any of 50 to 100 genes in the parasite, Wellems says. "It sounds as if at long last we have a plausible explanation for how this hemoglobinopathy might protect against malaria," says Geoffrey Pasvol, a malaria
MAPPING PROTECTION The gene frequencies of hemoglobin C in West Africa (shown in shades of red), based on a simple diffusion model, overlap with areas where malaria is endemic or that are prone to malaria epidemics.
SURFACE STORY Malaria-parasite-infected red blood cells containing hemoglobin C (right) have fewer knoblike protrusions with PfEMP-1 than infected cells containing normal hemoglobin A (center). An uninfected red blood cell with hemoglobin A (left) is shown for comparison. The insets are confocal microscope images of the cells prior to being imaged with atomic force microscopy.
They find that hemoglobin C reduces the expression of a cytoadherence protein called PfEMP-1. The parasite displays this protein on the surface ofhost red blood cells in knoblike pro trusions. The protein enables inWWW.CEN-0NLINE.ORG
the red blood cell's cytoskeleton in a way that hinders the parasite from placing PfEMP-l normally on its host red cell. "Ifwe can find ways to interfere with the normal function of this major surface cy toadherence protein, we may have
expert at Imperial College Lon don in Middlesex, England. "While this has been shown for hemoglobin C, it might well ap ply to the [other hemoglobin vari ants}, such as S and Ε and thal assemia."—CE LI A HENRY C & E N / J U N E 2 7 , 2005
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