People who lack a cell surface protein called CCR5 are highly resistant to infection by HIV but may be at increased risk of developing West Nile virus (WNV) illness when exposed to the mosquito-borne virus, report researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
The study, by Philip M. Murphy, M.D., and colleagues, appears online in The Journal of Experimental Medicine. The findings may have cautionary implications for physicians who are treating HIV-positive individuals with experimental CCR5-blocking drugs, say the scientists.
"This is the first genetic risk factor to be identified for West Nile virus infection," says NIH Director Elias A. Zerhouni, M.D. "While infection does not always lead to illness, the virus can sometimes cause serious problems and, according to the Centers for Disease Control and Prevention, there were 102 deaths in the United States from West Nile virus infection in 2005."
"A decade ago, a number of research groups, including Dr. Murphy's, determined that CCR5 is the primary co-receptor used by HIV to infect cells," says NIAID Director Anthony S. Fauci, M.D. "Their work laid the foundation for the development of CCR5-blocking drugs, which are designed to slow the spread of HIV from cell to cell."
Most people inherit two normal copies (one from each parent) of the gene that codes for CCR5 protein. About 1 percent of North American whites, however, have a mutation in both copies (are homozygous) and thus do not produce any CCR5. These individuals have the good fortune of being highly resistant to HIV infection and otherwise seemed to suffer no ill effects from the absence of this receptor protein, scientists noted. But the new research by Dr. Murphy's team suggests that lacking CCR5 may not be an unalloyed good after all.
In 2005 Dr. Murphy and his coworkers developed a mouse model to clarify the roles of various immune system cells in responding to WNV infection. They discovered that while most mice survived WNV infection, mice genetically engineered to lack CCR5 receptors suffered rapid and uniformly fatal infection by the virus. Further investigation showed that CCR5 promoted the movement of several classes of immune system cells into the brain and central nervous system, which appeared to protect normal mice from the encephalitis (brain inflammation) characteristic of serious WNV infection.