Brain Virus May Give Clues to Causes Underlying Psychiatric and Neurological Problems

A Yale researcher tracing a recombinant virus as it entered the brains of laboratory animals found it damaged selective areas and then vanished without a trace, raising questions about possible mental problems caused by undetected viruses.

“The virus went to areas of the brain that play an important role in functions related to attention,” said Anthony Van den Pol, professor of neurosurgery at Yale School of Medicine and lead author of the study published as the cover story in the February issue of the Journal of Virology. “After a few days the virus was eliminated by the immune system, leaving no trace of the virus in the brain, but nerve cells in very specific areas of the brain were lost. This is a potential model for viruses that can cause psychiatric and neurological dysfunction, yet leave no evidence of their presence at later times.”

Co-authors of the study were Kevin Dalton and John Rose.

Van den Pol’s experiment involved laboratory rodents and a common laboratory virus, vesicular stomatitis virus (VSV), which is not dangerous to humans. The virus was designed to include a reporter gene, which enabled him to follow its path through the brain. Some of the laboratory animals used in the study inhaled the virus, and others received a microinjection in the brain.

When inhaled, the virus infects the olfactory system of the nose and then enters the brain through the olfactory nerve. In developing rodents, the virus continues into the rest of the brain. In mature rodents, cells within the olfactory system manage to halt the further movement of the virus to other brain regions.

If VSV gets past the olfactory system, one area of the brain for which the virus has an affinity is the dorsal raphe, the origin of much of the serotonin in the brain. A number of psychiatric drugs, for instance, the “SSRI” drugs used to treat depression, anxiety,and obsessive compulsive disorder, act by increasing serotonin in the brain. In contrast, this virus first blocks serotonin synthesis, and then may kill the serotonin neuron. Laboratory rodents exposed to the virus show learning and attention deficits.

In regions of the world where the virus is endemic, it does not raise human health concerns. In fact, by using molecular methods to design a recombinant VSV that includes genes from more dangerous viruses, VSV can be used beneficially to generate immunity against these other viruses.

“This virus can cause permanent changes in rodent behavior, lasting long after the virus is destroyed by the immune system. Developing brains show an enhanced sensitivity to VSV infection,” he said. “We do not know what causes many psychiatric and neurologic disorders. A hypothesis we are addressing with this model is that some of these diseases could be caused by short term infections of the brain by viruses that leave behind no molecular footprint, but generate a subtle trail of cell loss in discrete regions of the brain.”