Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New ways to disarm deadly South American hemorrhagic fever viruses

09.03.2010
New World hemorrhagic fevers are emerging infectious diseases found in South America that can cause terrible, Ebola-like symptoms. Current treatments are expensive and only partially effective.

Now, Howard Hughes Medical Institute (HHMI) researchers have discovered exactly how one type of New World hemorrhagic fever virus latches onto and infects human cells, offering a much-needed lead toward new treatments.

"New World hemorrhagic fevers are nasty, serious, and often fatal diseases," says Stephen C. Harrison, an HHMI investigator at Harvard Medical School and senior author of the report, published March 7, 2010, in Nature Structural & Molecular Biology. "The need for new interventions is high."

Arenaviruses, the infectious agents that cause New World hemorrhagic fevers, circulate naturally in rodents and can infect people who are in close contact with the animals. Symptoms include severe inflammation and bleeding from the mouth, nose, eyes, and other orifices. Most outbreaks occur in rural regions of Bolivia, Venezuela, Argentina, and Brazil. "The outbreaks of New World hemorrhagic fever tend to be brief and brutal, with mortality rates of 20 to 30 percent," says Jonathan Abraham, an M.D./Ph.D. candidate at Harvard University and first author of the paper. "These viruses aren't a huge public health issue yet, but you could say the New World hemorrhagic fevers are an emerging disease threat."

Researchers have known about these viruses since the 1960s, but the molecular basis of the disease has only been tackled recently, says Abraham, whose graduate studies are funded by HHMI through a Gilliam Fellowship for Advanced Study. The Gilliam Fellowships program currently supports the doctoral education of 30 exceptional students from disadvantaged backgrounds.

In 2007, Abraham was working with Boston Children's Hospital virologist Hyeryun Choe when he was co-first author on a report in Nature identifying the human cell surface receptor that the Machupo virus, an arenavirus, grabs to gain access to the human cell it is infecting. The receptor, called transferrin receptor 1, offers a handhold for Machupo virus as it invades cells in the body. Nearly every human cell displays the transferrin receptor, which ferries iron into cells.

Abraham then brought the project to Harrison, who had mentored the young scientist in 2004 as part of HHMI's Exceptional Research Opportunities Program (EXROP), which places undergraduate students from disadvantaged backgrounds in the laboratories of HHMI investigators and HHMI professors. The pairing was fortuitous. In Choe's laboratory, Abraham had developed methods to produce the Machupo virus 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 17 viruses produce surface proteins that are unable to bind to the human transferrin receptor, Harrison says.

For Abraham, the idea of finding a treatment for these New World hemorrhagic fevers is close to his heart. His family hails from Haiti, where there is a "huge burden of infectious diseases. I'd like to dedicate my career to studying pathogens in underserved parts of the world," he says.

Andrea Widener | EurekAlert!
Further information:
http://www.hhmi.org

Further reports about: HHMI Medical Wellness Nature Immunology hemorrhagic fever human cell

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>