West Nile Virus Neuroinvasive Disease

West Nile virus (WNV), first recognized in North America in 1999, was responsible for the largest arboviral epidemic of human encephalitis in history and continues to be the most frequent cause of epidemic meningoencephalitis in North America. WNV neuroinvasive disease (WNND) occurs in fewer than 1% of infected individuals, with presentations including aseptic meningitis, encephalitis, and poliomyelitis. Between 1999 and 2009, over 12,000 cases of WNND were reported in the United States, with the peak annual incidence occurring in epidemics of 2002 and 2003. In this review, we first summarize the epidemiology of WNV over the past decade and the salient clinical features of WNND, including a discussion of laboratory and radiographic findings, risk factors, morbidity, and mortality. In addition, we review recent progress in our understanding of virus and host determinants of the pathogenesis of WNND, as well as the prospects for the development of specific therapeutic targets.