Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists show that tick-borne flaviviruses use a novel mechanism to evade host defenses

29.09.2005


Researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have made the surprising discovery that flaviviruses, which cause such serious diseases as West Nile fever, yellow fever and forms of encephalitis, evade immune system defenses in different ways depending on whether they are transmitted by mosquitoes or ticks. This finding could lead to new approaches to developing vaccines and treatments against these illnesses.



"Flaviviruses exact an enormous toll in terms of illness and death worldwide," notes NIAID Director Anthony S. Fauci, M.D. "Because this is a relatively new field of study, everything we learn about how these viruses operate is significant. This elegant work opens an array of new questions and research opportunities to pursue as we strive to better understand this family of viruses and develop countermeasures against them."

Mosquito-borne flaviviruses include West Nile virus, yellow fever virus, dengue virus and Japanese encephalitis virus; the less-familiar tick-borne flaviviruses are just as serious, causing tick-borne encephalitis or hemorrhagic fevers. Currently, a Japanese encephalitis outbreak is raging in India and Nepal and has killed more than 1,000 people. In Europe and Southeast Asia, tick-borne encephalitis typically results in more than 10,000 patient visits to hospitals annually and has a fatality rate of up to 25 percent in some regions. Viruses that cause encephalitis lead to inflammation of the brain. Hemorrhagic fevers are viral infections that cause capillaries to burst, leading to unusual bleeding on or under the skin or in various organs.


The study released this week online in the Journal of Virology describes how a single virus protein--NS5--from the tick-borne Langat flavivirus counteracts the natural ability of interferon to combat the virus. Langat virus was originally isolated in the 1950s in Malaysia and Thailand. Langat virus can infect people following a tick bite, but there are no cases of natural disease recorded. In the 1970s Langat was briefly used as a live vaccine against more virulent tick-borne encephalitis viruses in Russia but caused encephalitis complications in about 1 of every 10,000 people.

Interferon, the body’s first defense against many viruses, triggers a cascade of immune defenses. According to researchers at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, MT, NS5 blocks the body’s attempt to signal for immune defenses, preventing the immune system from both stopping the spread of virus and helping the body recover from infection.

Interferon is so critical for recovery from these infections that it is being tested in clinical trials to treat infection with various flaviviruses. But the treatment appears to fail in about half of cases. Dengue virus, West Nile virus and yellow fever virus have a protein called NS4B that prevents interferon from functioning properly. It was thought that the tick-borne flaviviruses would use the same protein, so the NS5 finding was unexpected.

The RML group, directed by Marshall Bloom, M.D., chose Langat virus because it is spread by ticks--a trademark of RML expertise--and because it possesses the same survival mechanisms as the more serious tick-borne encephalitis, Omsk hemorrhagic fever (found in western Siberia) and the closely related Kyasanur forest disease (found in western India).

"These diseases are spread by the same tick that carries Lyme disease in the U.S.," says Dr. Bloom. "So, the fact that West Nile virus first appeared or emerged in the U.S. in 1999 should warn us about the potential for tick-borne flaviviruses to emerge on other continents." In preparation for such a development, Dr. Fauci notes that two other NIAID laboratories have similar flavivirus studies under way, and the three groups are building on the discoveries of each other.

Dr. Bloom says that all flaviviruses have a similar genomic structure, and many scientists thought they would use the same survival mechanism and respond to the same vaccines and therapies, but the RML work shows otherwise.

"NS5 prevents interferon from doing its sentry job and allows the virus to take over cells," says Dr. Bloom. "This is the first definitive study that dissects where the failure occurs in the signaling pathway, and then identifies some of the interacting partners in the cell and virus." Prior to this work, Dr. Bloom says, scientists knew only that NS5 helped tick-borne flaviviruses replicate.

RML’s Sonja Best, Ph.D., who spearheaded the Langat virus work, says the group will continue to study tick-borne flaviviruses by examining the role and location of NS5 in Powassan virus. Powassan virus, found in North America, Russia, China and Southeast Asia, rarely infects people but is potentially fatal. If the research group can track the movement of NS5 in Powassan-infected cells and learn how it interacts with other proteins to block immune defenses, "that would provide a target for therapeutics to counteract tick-borne flaviviruses," says Dr. Best.

Ken Pekoc | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht Light-driven reaction converts carbon dioxide into fuel
23.02.2017 | Duke University

nachricht Oil and gas wastewater spills alter microbes in West Virginia waters
23.02.2017 | Rutgers University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Organ-on-a-chip mimics heart's biomechanical properties

23.02.2017 | Health and Medicine

Light-driven reaction converts carbon dioxide into fuel

23.02.2017 | Life Sciences

Oil and gas wastewater spills alter microbes in West Virginia waters

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>