CCR5+ mononuclear cells (black) infiltrate the brain and help eliminate WNV infection.

Although West Nile virus (WNV) infections have made headlines in recent years, little is known about how the virus causes disease or how the immune system fights back. On page 1087, Glass and colleagues show that immune cells must invade the central nervous system to combat the virus, and the chemokine receptor CCR5 is their entry ticket into the brain.WNV is an RNA virus that attacks the brain and can cause meningitis and encephalitis. Although infections with WNV can be fatal, most cases are mild or asymptomatic, suggesting that the immune system is capable of fighting off the virus. But the details of the anti-WNV immune response remain poorly characterized.

Glass and colleagues now show that WNV infection in mice triggers an influx of T cells, natural killer cells and macrophages into the brain in response to local production of chemokines. The influx of cells, which protected the mice against lethal infection, largely depended on the expression of CCR5 on the responding cells. In CCR5-deficient mice, fewer cells gained access to the brain and the infection was uniformly fatal.

To determine whether CCR5 is equally important for combating WNV infection in humans, the authors are now testing whether people who had severe or fatal infections with WNV were more likely to carry the CCR5 deletion mutation. This mutation is best known for its ability to protect against HIV infection, as CCR5 is a cellular coreceptor for HIV.