Rabies races up nerve cells

The rabies virus may take the express train to the brain.

By hijacking a transporter protein and hitting the gas, the disease-causing rabies virus races up long nerve cells that stretch through the body, researchers report August 28 in PLOS Pathogens.

The new work “is very promising,” says virologist Monique Lafon of the Pasteur Institute in Paris, and could give researchers another target in their search for therapies against rabies infections.

With a fatality rate near 100 percent — higher than Ebola — rabies stands among the most deadly diseases in the world. The virus lurks in the saliva of infected animals and passes to humans most commonly through a bite. Then it steals up the nerves and into the brain, killing cells and often triggering bizarre behaviors, such as hyperactivity and a fear of water.

A vaccine can block the infection, but only if given to patients soon after a rabid animal’s bite. Once the virus creeps into the nerves, it’s pretty much unstoppable, Lafon says. “We need to find antivirals that can block the progression of the virus.”

Scientists knew that the virus hitchhiked up nerve cells instead of cruising through the bloodstream, but until now no one had been able to get a good look at this long-distance travel, says Harvard virologist Silvia Piccinotti.

By adopting a microfluidics technique used in physics and engineering, the scientists were able to mimic on a silicone wafer the movement of virus particles in the body. After growing mouse nerve cells on the penny-sized wafer, neurobiologists Shani Gluska and Eran Perlson of Tel Aviv University in Israel and colleagues infected the neurons with rabies. Then the team tracked the viruses’ journey through the long, skinny mouse cells, as well as the paths of proteins known to latch onto the virus.

One such protein, called p75NTR, normally carries molecules important for nerve cell survival. But when p75NTR traveled with the virus, the protein shuttled the disease-causing particles up nerves even faster than usual, the team found. “Rabies virus kidnaps and manipulates the cells’ transport machinery,” Perlson says.

The virus rides with p75NTR in little acidic bubbles and somehow forces the protein to speed up. Getting a lift with p75NTR is only one method the virus uses to travel up nerve cells, but it seems to be the rapid transit system for rabies, Perlson says.

Future antivirals could target p75NTR, Lafon notes, in addition to other cellular proteins the rabies virus exploits to get to the brain.

The findings also help explain how transportation works in nerve cells, Perlson says, which could aid scientists studying diseases in which nerves have trouble delivering cargo, such as amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s.