Abstract
West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in terms of human clinical manifestations, host immune responses, neuroinvasion, and therapeutic interventions.
Highlights
West Nile virus (WNV)-associated neuroinvasive disease affects all ages, elderly and immunocompromised individuals are at risk
Using the host cellular machinery, the viral RNA genome trafficks through the cytosol to the endoplasmic reticulum (ER), where the viral RNA is translated as a polyprotein that is cleaved into ten functional proteins by both cellular and viral proteases
WNV fever and neuroinvasive disease: WNV infection in humans can result in a spectrum of diseases ranging from a febrile illness classified by the Centers for Disease Control and Prevention (CDC) as WNV fever to severe neuroinvasive disease classified as meningitis, encephalitis, or acute flaccid paralysis [16]
Summary
WNV transmission is maintained in a cycle between Culex mosquitoes, the major vector, and a variety of bird species, the major reservoir hosts. About 1 in 150 people who are infected with WNV develop a severe illness affecting the central nervous system (CNS), such as encephalitis and meningitis. WNV has spread across six of seven continents, including Africa, Asia, Europe, Australia (subtype Kunjin), North America, and South America. It is considered one of the most important causative agents of human viral encephalitis worldwide. 1999, WNV has been estimated to cause more than 6 million human infections [13], with over 24,000 neurological disease cases and 2300 deaths in the U.S In addition, in 2018, a large outbreak occurred in Europe involving over 2000 human cases in 15 countries [15]. There is an urgent need to understand in-depth the pathogenesis of WNV and develop specific treatment strategies
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