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FLVCR-like proteins may contribute to malaria control

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52nd ASH Annual Meeting

ORLANDO — Modulation of anopheline feline leukemia virus subgroup C receptor–like proteins may serve as a means of controlling malaria, according to findings presented here.

John G. Quigley, MD, of the department of medicine at the University of Illinois at Chicago, and colleagues hypothesized that modulation of the heme export function of the cell-surface protein, feline leukemia virus subgroup C receptor (FLVCR) would increase mosquito mid-gut oxidative stress and impact Plasmodium transmission.

For the study, researchers identified FLVCR-like proteins in a number of blood-feeding disease vectors and then went on to isolate anopheline orthologs of FLVCR from the two prevalent malaria-transmitting mosquitoes: Anopheles gambiae and Anopheles stephensi.

Comparisons of the expression of human FLVCR in mosquitoes were conducted before and after a blood meal.

Results indicate that following exposure to heme, the heme export protein was highly expressed on the surface of gut cells.

“Importantly, knockdown of A. stephensi FLVCR in mosquitoes decreases midgut FLVCR protein levels after a blood meal by ~30% with a concomitant increase in midgut oxidative stress levels, which may be sufficient to impact malaria pararsite transmission," Quigley told HemOnc Today.

The researchers are currently evaluating the effects of antibodies to mosquito FLVCR, or dsRNA–mediated blockade of A. stephensi FLVCR heme export function on Plasmodium oocyst survival, salivary gland sporozoite development, mosquito midgut reactive oxygen species production and mosquito fecundity.

“This study is still ongoing, but we are hopeful that inhibiting the function of this protein may have an impact on Plasmodium transmission without affecting mosquito survival. In that case, mosquito FLVCR proteins could serve as potential vaccine targets in the fight to control malaria,” the researchers wrote.

For more information:

• Quigley J. #2. Presented at: 52nd ASH Annual Meeting; Dec 4-7, 2010; Orlando.

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