How the Rabies Virus Makes Animals “Mad”

Rabies virions are bullet-shaped with 10-nm spike-like glycoprotein peplomers covering the surface. The ribonucleoprotein is composed of RNA encased in nucleoprotein. (Source: CDC)

A virus has no brain, but sometimes their adaptations seem so devious, one might suspect them of conspiracy.

New research into how the rabies virus affects the brain and behavior of an infected host serves as an example. The rabies virus, primarily spread through animal bites, affects cattle and is one of the best-known zoonotic diseases, killing more than 50,000 people annually.

Noting that the pathogenesis of the disease remains poorly understood, researchers at the University of Alaska – Fairbanks engaged in research to explain how the virus affects the brain of a host. Their report, titled “Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS,” is published in the journal Scientific Reports.

As we know, animals infected with rabies demonstrate drastic changes in behavior, becoming far more aggressive and less fearful than normal, exemplified by the image of a “mad dog.” That behavior increases the chance the host will bite another animal, thereby spreading the virus to a new host before the original host succumbs to the disease.

Earlier research has shown that glycoprotein molecules on the surface of the rabies virus bind to nicotinic acetylcholine receptors in muscles. Knowing that mammalian brains also contain nicotinic acetylcholine receptors, the Alaska researchers set out to determine whether the virus could inhibit those neurotransmitter receptors and affect host behavior. They tested their hypothesis in-vitro, in roundworms (C. elegans) and in mice. They found that such binding does occur, and “a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behavior in animals through inhibition of nicotinic acetylcholine receptors present in the central nervous system.”

This finding, they report, provides a novel aspect to virus receptor interaction and host manipulation by pathogens in general, and the results “provide a mechanistic explanation for the behavioral changes in hosts infected by rabies virus.”

The researchers hope that better understanding of the mechanisms through which the rabies virus affects its host will lead to new strategies for treating the disease.

Read the full article from Scientific Reports.