Defenses down: mutation boosts West Nile risk.

A genetic mutation has been identified that increases a person's susceptibility to West Nile virus, a new study indicates. Ironically, this mutation had previously been shown to provide a barrier against HIV, the virus that causes AIDS.

The protein eliminated by the mutation was previously thought to be useless and even a liability. The new finding suggests that it might be an essential weapon in fending off the mosquito-borne virus, says Philip M. Murphy, an immunologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

West Nile virus is most dangerous to elderly people and others who have compromised immune systems. Although 80 percent of infections go unnoticed, the virus caused illness in 2,819 people in the United States in 2005, leading to encephalitis or meningitis in 1,189 of them and killing 105, according to the Centers for Disease Control and Prevention in Atlanta.

The mutation that has been implicated in West Nile disease susceptibility shuts down the production of a protein called chemokine receptor-5 (CCR5). This protein is the primary cell-surface receptor that is commandeered by HIV, which uses it to enter white blood cells. The mutation that prevents CCR5 production renders 1 percent of whites highly resistant to infection by HIV but hasn't been found in other races. Scientists had reasoned that people were better off without CCR5.

In the new study, Murphy and his colleagues worked with researchers in Arizona and Colorado to analyze blood and spinal-fluid samples from 395 people in those states who had been infected with West Nile virus.

The CCR5 mutation showed up in more than 4 percent of the West Nile patients but in only 1 percent of 1,318 healthy blood donors used as a comparison group, the researchers report in the Jan. 17 Journal of Experimental Medicine.

"This appears to be a reasonably careful analysis" of this mutation in people with and without West Nile infections, says Richard A. Kaslow, an infectious-disease physician at the University of Alabama at Birmingham.

In people with the mutation, lacking the CCR5 protein may lead to "a brain infection from West Nile that is not well controlled," Murphy says.

In a study of mice reported in the Oct. 17, 2005 Journal of Experimental Medicine, Murphy's team found that all animals genetically engineered to lack CCR5 died when exposed to West Nile virus. However, normal mice fended off the virus by producing extra CCR5 proteins on the surface of white blood cells, which were ushered into the brain, where they protected against the infecting virus.

Several companies have designed drugs aimed at blocking CCR5, in an attempt to stop HIV from invading white blood cells. The approach mimics the protection against HIV conferred by the CCR5 mutation. The drugs are being tested in people.

The new findings suggest that people taking the CCR5-blocking drugs to prevent or quell HIV infection may need to take precautions to avoid West Nile disease, Kaslow says.

STATS

2,819

U.S. cases in which West Nile virus caused illness in 2005