Abstract
West Nile virus (WNV), like the dengue virus (DENV) and yellow fever virus (YFV), are major arboviruses belonging to the Flavivirus genus. WNV is emerging or endemic in many countries around the world, affecting humans and other vertebrates. Since 1999, it has been considered to be a major public and veterinary health problem, causing diverse pathologies, ranging from a mild febrile state to severe neurological damage and death. WNV is transmitted in a bird–mosquito–bird cycle, and can occasionally infect humans and horses, both highly susceptible to the virus but considered dead-end hosts. Many studies have investigated the molecular determinants of WNV virulence, mainly with the ultimate objective of guiding vaccine development. Several vaccines are used in horses in different parts of the world, but there are no licensed WNV vaccines for humans, suggesting the need for greater understanding of the molecular determinants of virulence and antigenicity in different hosts. Owing to technical and economic considerations, WNV virulence factors have essentially been studied in rodent models, and the results cannot always be transported to mosquito vectors or to avian hosts. In this review, the known molecular determinants of WNV virulence, according to invertebrate (mosquitoes) or vertebrate hosts (mammalian and avian), are presented and discussed. This overview will highlight the differences and similarities found between WNV hosts and models, to provide a foundation for the prediction and anticipation of WNV re-emergence and its risk of global spread.
Highlights
Since its first isolation in 1937 in the province of Uganda [1], West Nile virus (WNV) has been a leading cause of neuroinvasive diseases in humans [2]
Audsley and colleagues [91] created chimeric viruses between an IC derived from the North American isolate WNV NY99 4132, isolated in 1999 in New York City, and the Kunjin virus (KUN) virus, and more between their 5 untranslated regions (UTRs) and 3 UTR non-coding regions
Because the Asp483 residue is highly conserved among flaviviruses causing encephalitis, such as WNV, TBEV, or JEV, but not in dengue or yellow fever viruses associated with hemorrhagic syndromes [132], it was considered as a possible determinant of neurovirulence and/or neuroinvasion
Summary
Since its first isolation in 1937 in the province of Uganda [1], West Nile virus (WNV) has been a leading cause of neuroinvasive diseases in humans [2]. Neuroinvasive diseases were diagnosed in horses and in humans in South Africa These were associated with infection by lineage 2 strains of the WNV [35]. The virus crosses the midgut barrier and diffuses in the hemolymph to other organs, including the salivary glands, whose infection is a prerequisite for WNV transmission to new susceptible vertebrate hosts (Figure 2). It has been known for years that the genome of positive-strand RNA viruses, like flaviviruses, can be infectious when introduced into susceptible cells by transfection [77] On this basis, reverse genetic technology permits manipulation of viral genomes and analysis of consequent changes in viral pathogenesis, as well as virulence, cell response to new epizootics. The aim is to highlight the determinants that are specific to a given host, as well as those that the host have in common, in order to provide a better understanding of WNV virulence and to provide a foundation on which measures to control WNV spread and outbreaks can be proposed
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