Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antiviral compound may protect brain from pathogens, West Nile virus study shows

18.05.2015

Researchers have found that an antiviral compound may protect the brain from invading pathogens.

Studying West Nile virus infection in mice, scientists at Washington University School of Medicine in St. Louis showed that interferon-lambda tightens the blood-brain barrier, making it harder for the virus to invade the brain.


Mosquitoes are known to infect people and animals with West Nile virus. Studying West Nile virus infection in mice, scientists at Washington University School of Medicine in St. Louis have shown that an antiviral compound tightens the blood-brain barrier, making it harder for the virus to invade the brain.

Credit: Centers for Disease Control and Prevention

The blood-brain barrier is a natural defense system that is supposed to keep pathogens out of the brain. Sometimes, however, bacteria or viruses circulating in the blood slip past the blood-brain barrier, turning routine illnesses into serious infections.

Interferon-lambda is produced naturally in the body in response to infection, but the new research suggests that larger amounts of the antiviral compound may tighten the blood-brain barrier against pathogens or possibly even faulty immune cells that can attack the brain and cause conditions such as multiple sclerosis.

By blocking interferon-lambda's receptors in the brain, it may be possible one day to open the barrier to chemotherapies to treat specific diseases in the brain, such as tumors. Such tumors now are not optimally treated with chemotherapy drugs because the drugs can't cross the blood-brain barrier.

The findings are available online in Science Translational Medicine. Follow the School of Medicine on Facebook, Twitter and Google+.

"We have identified a new antiviral function of interferon-lambda that doesn't involve directly attacking a virus but stems viral invasion into the brain," said co-senior author Robyn Klein, MD, PhD, professor of medicine. "This suggests the possibility of multiple new applications. We're testing one of these right now, conducting studies in mice to see if interferon-lambda can help prevent brain inflammation in a mouse model of multiple sclerosis."

Other forms of interferon have shown potential for influencing the blood-brain barrier, but interferon-lambda may have significantly fewer side effects.

Infections with West Nile virus occur globally. No treatments exist for the virus, which crosses the blood-brain barrier in an estimated 1 percent of infected people, causing a debilitating neurological condition that can be fatal.

Klein and co-senior author Michael Diamond, MD, PhD, professor of medicine, looked closely at West Nile virus infections in mice to learn more about how viruses cross the blood-brain barrier. This barrier typically keeps large molecules, such as immune cells, drugs and pathogens, out of the brain while letting in essential nutrients such as glucose.

In earlier research, Klein showed that West Nile virus can open the blood-brain barrier to enter the central nervous system, but that the barrier usually quickly closes, preventing immune molecules from following to attack the virus.

In the new study, the scientists studied mice that lacked the interferon-lambda receptor. Compared with normal mice, the mice without the receptor had higher levels of West Nile virus in the brain. The researchers found the blood-brain barrier was much more permeable to the virus in these mice, suggesting that loss of the receptor through which interferon-lambda acts had loosened the barrier.

The scientists then gave normal mice West Nile virus along with interferon-lambda. The mice received the antiviral compound at the start of the infection and two and four days later. Typically less than 20 percent of normal mice survive such a high dose of the virus, but survival rates rose to more than 40 percent after treatment with interferon-lambda.

"Viruses are most dangerous when they enter the brain," said Diamond. "Compared with untreated mice, we found significantly lower concentrations of the virus in the brain among mice treated with interferon-lambda."

If further studies of interferon-lambda prove fruitful in stemming the spread of viruses to the brain, a major hurdle remains. By the time symptoms of viral infections are serious, the virus is already in the brain. This reality suggests earlier diagnosis is critical.

But, the researchers note, interferon-lambda may be a better way to influence what gets into the brain than other forms of interferon, which are associated with significant side effects such as fever, chills and fatigue.

"Interferon-lambda has significantly fewer receptors in the body, which may mean using it as a treatment is likely to have fewer side effects," Diamond said. "It's also possible that interferon-lambda may influence other protective barriers in the body, such as those in the skin and the gut, an area of research my laboratory is investigating."

###

This work was supported by the National Institutes of Health (NIH), grant numbers U19 AI083019, PCTAS AI083019-0251, T32-AI007172, RO1 AI074973, RO1 NS052632 and F31-NS07866-01, and the National Science Foundation, grant number DGE-1143954. Lazear HM, Daniels BP, Pinto AK, Huang AC, Vick SC, Doyle SE, Gale Jr. M, Klein RS, Diamond MS. Interferon-lambda restricts West Nile virus neuroinvasion by tightening the blood-brain barrier. Science Translational Medicine, online April 22, 2015.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Media Contact

Judy Martin Finch
martinju@wustl.edu
314-286-0105

 @WUSTLmed

http://www.medicine.wustl.edu 

Judy Martin Finch | EurekAlert!

More articles from Health and Medicine:

nachricht A 'half-hearted' solution to one-sided heart failure
24.11.2017 | Boston Children's Hospital

nachricht New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>