1. ¹Department of Pathology, School of Medical Sciences, Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia
2. ²The Children's Hospital at Westmead, Westmead, NSW and Department of Paediatrics and Child Health, Faculty of Medicine, The University of Sydney, Sydney, New South Wales, Australia

Correspondence: Professor NJC King, Department of Pathology, School of Medical Sciences, Bosch Institute, The University of Sydney, Blackburn Bldg D06, Sydney, New South Wales 2006, Australia. E-mail: nickk@pathology.usyd.edu.au

³Current address: Department of Dermatology, Faculty of Medicine, The University of Sydney, Sydney, New South Wales 2006, Australia

⁴Current address: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA

Received 24 September 2006; Accepted 5 October 2006; Published online 5 December 2006.

Abstract

With the recent emergence of the flavivirus, West Nile virus (WNV), in particular, the New York strain of Lineage I WNV in North America in 1999, there has been a significant increase in activity in neurotropic flavivirus research. These viruses cause encephalitis that can result in permanent neurological sequelae or death. Attempts to develop vaccines have made progress, but have been variably successful, despite considerable commercial underwriting. Thus, the discovery of ways and means to combat disease is no less urgent. As such, most recent work has been directed towards dissecting and understanding the pathogenesis of disease, as a way of informing possible approaches to abrogation or amelioration of illness. Whether inherent to flaviviruses or because humans are incidental, dead-end hosts, it is clear that these viruses interact with their human hosts in extremely complex ways. This occurs from the cellular level, at which infection must be established to produce disease, to its interaction with the adaptive immune response, which may result in its eradication, with or without immunopathological and consequent neurological sequelae. As human proximity to and contact with flavivirus insect vectors and amplifying hosts cannot practically be eliminated, our understanding of the pathogenesis of flavivirus-induced diseases, especially with regard to possible targets for treatment, is imperative.