An antiviral compound can tighten the blood-brain barrier, making it harder for the West Nile virus to invade the brain, scientists have found.
The antiviral compound, interferon-lambda, is produced naturally in the body in response to infection.
The new research suggests that larger amounts of the 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.
Scientists at Washington University School of Medicine in St Louis believe that 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 tumours.
Such tumours now are not optimally treated with chemotherapy drugs because the drugs can't cross the blood-brain barrier.
"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, 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," Klein said.
Klein and co-senior author Michael Diamond, 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 per cent of normal mice survive such a high dose of the virus, but survival rates rose to more than 40 per cent after treatment with interferon-lambda.
"Compared with untreated mice, we found significantly lower concentrations of the virus in the brain among mice treated with interferon-lambda," said Diamond.
