Rabies is a disease caused by a virus that targets the brain and nervous system once it gets into a new host, usually via the bite of an infected animal. Now new research led by Tel Aviv University in Israel has discovered the molecular mechanism that the virus uses to get from the bite wound to the brain as quickly as possible.
The researchers report their findings in the journalPLOS Pathogens.
Rabies, which causes inflammation in the brain and spinal cord, is almost always fatal if not treated early. According to the World Health Organization, rabies occurs in more than 150 countries, and kills over 60,000 people every year, mostly in Asia and Africa.
Many disease pathogens spread through the body via the bloodstream, powered along by the pumping of the heart. But those that travel outside the bloodstream have to use some other means of transport.
Rabies virus uses the network of nerve cells that link all parts of the body to the brain. In particular, it makes use of nerve cells in the peripheral nervous system, which connects various parts of the body to the central nervous system that comprises the brain and the spinal cord.
Axons or fibers in the peripheral nervous system can be hundreds of times longer than the cell bodies they belong to, and not only do they transport electrical signals they also transport molecules over long distances in the body.
For their study, senior author Dr. Eran Perlson, of Tel Aviv’s Sackler Faculty of Medicine and Sagol School of Neuroscience, and colleagues were particularly interested in a protein called the p75NTR receptor, which is found on the tips of peripheral neurons.
They discovered that the rabies virus uses the receptor in the same way as another small molecule called NGF or nerve growth factor. NGF binds to p75NTR, where it is absorbed into the neuron and travels to the cell body in tiny acidic bubbles called vesicles.
Using a method called live cell imaging, the team saw how the rabies virus entered at nerve terminals and traveled along axons.
Rabies virus needs to bind to p75NTR receptor to get to brain quickly
To test how important the receptor might be to the virus, the researchers grew nerve cells that had no p75NTR. They found while the virus was able to travel along the axons without p75NTR, it did so far less effectively: progress was slow, erratic, and infrequent, and the vesicles sometimes even went in the wrong direction.
The team concluded that for fast and effective transport, the rabies virus needs to be accompanied by the p75NTR receptor.
They found when bound to p75NTR, the virus traveled about 8 cm per day, which is about 40% faster than the speed at which the receptor travels when bound to its regular partner, NGF.
The authors conclude that their findings show not only does the rabies virus hijack the transport system of neurons, but it also appears to “manipulate the axonal transport machinery to facilitate its own arrival at the cell body, and from there to the central nervous system at maximum speed.”
Source: MNT – Medical News Today