New ways found to tackle deadly South American hemorrhagic fever viruses

surface protein, which links to the human transferrin receptor. Meanwhile, Harrison had stocks of purified transferrin receptor because he had previously worked to image the molecule and understood its molecular structure.

Together, the pair made batches of the Machupo surface protein bound to the transferrin receptor and then set about creating an image showing how the two molecules connected. They used X-ray crystallography, a technique in which protein crystals are bombarded with x-ray beams. As the X-rays pass through and bounce off of atoms in the crystal, they produce a diffraction pattern, which can then be analyzed to determine the three-dimensional shape of the protein. After a data collection trip to the powerful X-ray beam at Argonne National Laboratory in Illinois, Abraham and Harrison were able to examine the atomic structure of the Machupo surface protein attached to the transferrin receptor.

The images show that the Machupo surface protein binds to the transferrin receptor in a surprising way — using a loop called the apical domain. The biological function of this loop in humans is unknown, Harrison says. Other segments of the receptor bind iron-bearing transferrin, but the apical domain appears to be uninvolved in that process. “We don’t know the normal function of the apical domain. Obviously it didn’t evolve just to give Machupo virus a way to infect humans, but that’s what the virus has evolved to latch onto,” he says.

Because the apical domain is not involved in the critical task of moving iron into cells, Harrison says it presents an attractive target for drugs. In theory, an antibody designed to attach to the apical domain would prevent the Machupo virus from attaching to cells, blocking infection. One possible treatment strategy, then, would be to infuse patients with such an antibody during the early stages of infection, which might slow the infection enough to let patients recover.

Harrison says the finding might also help virologists predict which of the 22 known arenaviruses might be capable of infecting humans. Only five are known to infect humans now—and all of those bind to the human transferrin receptor. Presumably the other seventeen viruses produce surface proteins that are unable to bind to the human transferrin receptor, Harrison says.