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Researchers ‘block’ the West Nile virus out of the brain by tightening the blood-brain barrier.

Researchers have found that an antiviral compound may protect the brain from invading pathogens.  Studying West Nile virus infection in mice, researchers at Washington University showed that interferon-lambda tightens the blood-brain barrier, making it harder for the virus to invade the brain.

The team explain that 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, the team hypothesize that it may be possible one day to open the barrier to chemotherapies to treat specific diseases in the brain, such as tumours. Such tumours now are not optimally treated with chemotherapy drugs because the drugs can’t cross the blood-brain barrier.

The current study has identified a new antiviral function of interferon-lambda that doesn’t involve directly attacking a virus but stems viral invasion into the brain.  This suggests the possibility of multiple new applications. The researchers are now 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.  They add, that 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.  The current study 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 previous studies the team showed that the 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 current 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 data findings showed that 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 researchers then gave normal mice the 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, explain the team.  Compared with untreated mice, they found significantly lower concentrations of the virus in the brain among mice treated with interferon-lambda.  They go on to add that 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.

However, the researchers note that 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.  The team state that because interferon-lambda has significantly fewer receptors in the body it may mean it has fewer side effects.

The researchers surmise that 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 the laboratory is now investigating.

Source:  Washington University School of Medicine

 

© 2012 Cambridge MedChem Consulting.
© 2012 Cambridge MedChem Consulting.

 

 

 

 

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