The Way Rabies Virus Works at the Molecular Level

Rabies is a viral disease which is transmitted from animals to humans through bites or scratches. The infected host becomes aggressive owing to the ability of the virus to alter behavior.

When rabies virus gets into a host, it attacks the central nervous system. In humans, it results in a variety of symptoms such as confusion, anxiety, agitation, hallucination, partial paralysis, and in its terminal stages, a fear for water – referred to as “hydrophobia”. Because of hydrophobia, the affected person gets frightened at the sight of water and refuses to drink. Ultimately, he or she dies.

A vaccination can prevent rabies. However, poorer sections in Asia and Africa usually are unable to avail these resources to keep the virus away. So, 95% of deaths worldwide owing to rabies occurs in these continents, says the World Health Organization (WHO).

The mechanism by which rabies virus hijacks the hosts’ brain has been intently studied since the early 19th century. However, it had remained unrevealed for a long time, but now researchers have found how this virus works at a molecular level.

The study
A team of scientists from the University of Alaska Fairbanks have carried out this study and found the action of the virus at the molecular level which alters the behavior of the host. It has been published in the journal Scientific Reports.

Dr. Karsten Hueffer, the study lead explains “Many infectious agents change behavior in their host, but we do not understand how they do this. Our study provides, for the first time, a detailed molecular mechanism for how an infectious agent induces specific behaviors.”

One of the reasons why rabies virus is thought provoking is that, this virus which has a relatively simple genetic composition can bewilder animals with surprisingly complex systems. Only five genes encoding very little info are present in the rabies virus. But there are over 20,000 genes in dogs, and they have sophisticated central nervous system and immune system. Even then, this virus can modify the behavior of the dog to lose its fear, get aggressive and bite, which permits the transmission of the virus through the animal’s saliva.

The researchers studied the previous research findings from the 1980s and 1990s to help in their research. These explain the way the viral molecules bind to the proteins (nicotinic acetylcholine receptors) that respond to the neurotransmitter acetylcholine — this in turn affects muscle control.

Studies from recent days also showed that a sequence of amino acids in the glycoprotein molecules in rabies resembles to an amino acid sequence present in snake venom. These snake venom amino acids are involved in inhibiting the nicotinic acetylcholine receptors.
The scientists knew that nicotinic acetylcholine receptors which are found in the muscles are also found in the brain. This helped them derive a connection between these existing findings. They understood that the factor which influenced the host’s bewildered behavior after an infection of the virus, was amino acids in rabies glycoprotein.

Dr. Karsten Hueffer puts it this way- “If snake venom has a similar structure to parts of the virus, and inhibits these receptors, we thought maybe the virus could also inhibit these receptors in the brain. Furthermore, we thought that this interaction could influence behavior.”

After noting this possible connection, to test this hypothesis, he carried out some experiments on mice, in collaboration with Dr. Michael Harris. They found that in the initial infection stages, the viruses gathered in the intercellular spaces between brain cells. These spaces serve as areas for communication between the brain cells.

They again hypothesized that if viruses bind to the receptors in these spaces, they can alter the normal communication of the brain cells and thus change the host’s behavior. To test this, they injected the mice’s brains with rabies glycoprotein. They also gave a control injection to another group of mice. They observed that the mice which received the rabies glycoprotein were significantly more agitated, just like the rabies-infected animals.

This is the first experimental evidence that demonstrates the way rabies interacts with other cells in the nervous system to induce a frenzied behavior, which in turn enables the spread of the virus through the infected hosts.

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