|
Discovery could lead to better control of hemorrhagic fever viruses
Researchers report discovering the receptor through which a group of life-threatening hemorrhagic fever viruses enter and attack the bodys cells, and show that infection can be inhibited by blocking this receptor. The findings, to be published online by the journal Nature on February 7, give a clue to the high lethality of New World arenaviruses, suggest a way of reducing the severity of infection, and point the way toward a sorely needed treatment strategy.The receptor, identified in Choes lab by Jonathan Abraham, PhD, an MD-PhD student at HMS, turned out to be transferrin receptor 1 (TfR1), a well-known protein that is key in enabling cells to take up iron. Additional studies, performed in Farzans lab by HMS graduate student Sheli Radoshitzky, confirmed that TfR1 is also the receptor for the other three New World arenaviruses. (Abraham and Radoshitzky are both first authors on the study.) Expertise from Nancy Andrews, MD, PhD, an expert in iron metabolism at Childrens, sped up the work. Although not all hemorrhagic fever viruses use TfR1 to enter the bodys cells, the discovery may help explain why these viruses wreak such havoc, damaging multiple organs and causing bleeding under the skin, in internal organs, and from orifices like the mouth, eyes or ears. Because of TfR1s essential function in transporting iron into cells, it is found on the surface of virtually every cell of the body. It is abundant on endothelial cells, which line blood vessels, a fact that may help account for the bleeding and organ damage caused by the viruses. TfR1 is also especially abundant on activated immune cells the very cells that mobilize to fight the viruses making them especially vulnerable to infection. Choe now hopes to translate these findings into treatments to contain natural or intentional outbreaks of New World hemorrhagic fever. Serendipitously, several anti-TfR1 antibodies have already been developed as anticancer therapeutics (cancer cells are also high in TfR1), and some have already been through clinical trials. Choes lab will test these antibodies, hoping to find one that inhibits virus entry without compromising TfR1s essential function in cellular iron uptake. The findings of Choe and colleagues also suggest that iron supplements may reduce the severity of New World virus infections. Past studies have shown that when the iron level in the body is low, the number of transferrin receptors in tissues increases. Consistent with these findings, Choes team found that New World arenaviruses infect cells more efficiently when iron levels are low, and that adding iron to cultured cells makes them less susceptible to infection. Choe notes that New World hemorrhagic fever outbreaks mostly occur in poor rural areas, where people are often deficient in micronutrients, including iron, possibly predisposing them to more severe infection when exposed to the rodents that carry the viruses. Posted by: DanNY 2007-02-09 |
| http://www.rantburg.com/poparticle.php?ID=179948 |