Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists block Ebola infection in cell-culture experiments

25.06.2009
Accomplishment could lead to first therapy for deadly disease

Researchers at the University of Texas Medical Branch at Galveston have discovered two biochemical pathways that the Ebola virus relies on to infect cells. Using substances that block the activation of those pathways, they've prevented Ebola infection in cell culture experiments — potentially providing a critical early step in developing the first successful therapy for the deadly virus.

Ebola inflicts severe and often fatal hemorrhagic fever on its victims, producing 90 percent mortality rates in some outbreaks. No vaccine exists for the virus, and it is considered a high-risk agent for bioterrorism. Natural Ebola outbreaks strike periodically, often with devastating effect; recent examples include outbreaks in Uganda in 2008 and the Democratic Republic of the Congo in 2007.

The UTMB team took a new approach to stopping viral infection, using powerful new computational and analytical techniques to focus more on the host cell than the virus, according to microbiology and immunology associate professor Robert Davey.

"The premise for this work is that the virus is essentially nothing without a cell," said Davey, lead author of a paper on the research appearing this month in the journal Drug Discovery Research. "It needs to rely on many cell proteins and factors for it to replicate. The idea is that if we can suppress the expression of those cell proteins for just a short time, we can then stop the disease in its tracks."

To identify the critical proteins, the UTMB researchers — including research scientist Andrey A. Kolokoltsov, assistant professor Mohammad F. Saeed, postdoctoral fellow Alexander N. Freiberg and assistant professor Michael R. Holbrook — first conducted large-scale screening experiments using sets of cells treated with small interfering RNA (siRNA) to block 735 different genes that might produce proteins important to Ebola infection. They then added Ebola "pseudotype" viruses, artificially created virus particles made by wrapping Ebola envelope proteins around a core of genetic material from another virus. (The resulting viruses behave just like Ebola when infecting a cell, but are safe enough to work with in an ordinary lab.)

"We got a number of hits, quite a lot of places where the virus wasn't infecting the cells," Davey said. "The problem was then to understand what those hits meant."

To make sense of the data, the researchers turned to a newly developed statistical algorithm designed especially to prioritize the results of siRNA screens. After subjecting that output to further computational analysis, they found that two networks of biochemical reactions seemed particularly important to Ebola's entry into cells: The PI3 kinase pathway and the CAMK2 pathway. Since drugs to block both pathways are available, the UTMB group decided to investigate whether they would interfere with Ebola infection of cells — first using virus pseudotypes, and then, in UTMB's maximum containment BSL4 "spacesuit" lab, with Ebola Zaire itself, the variety of the virus most associated with high mortality rates.

"With the real virus in the BSL4, we found that the PI3 kinase inhibitor dropped virus titers by 65 percent, and if we used drugs which block CAMK2 function, it was just killed — stopped dead," Davey said. "This is really, very, very interesting because this pathway has a lot of potential for future pharmaceutical exploitation."

Jim Kelly | EurekAlert!
Further information:
http://www.utmb.edu

More articles from Life Sciences:

nachricht Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo

nachricht Full of hot air and proud of it
18.04.2018 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>