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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>