ICAM-1 participates in the entry of West Nile virus into the central nervous system

Section of Infectious Diseases, Department of Internal Medicine; Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520; Department of Biomedical Sciences and Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, California 90048

^* To whom correspondence should be addressed. Email: erol.fikrig{at}yale.edu.

	Abstract

Determining how West Nile virus crosses the blood-brain barrier is critical to understanding the pathogenesis of encephalitis. Here we show that ICAM-1^-/- mice are more resistant than control animals to lethal West Nile encephalitis. ICAM-1^-/- mice have a lower viral load, reduced leukocyte infiltration and diminished neuronal damage in the brain compared to control animals. This is associated with decreased blood-brain barrier leakage after viral infection. These data suggest that ICAM-1 plays an important role in West Nile virus neuroinvasion and targeting ICAM-1 signaling may help control viral encephalitis.