Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts

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.

Pathogenesis of Two Western Mediterranean West Nile Virus Lineage 1 Isolates in Experimentally Infected Red-Legged Partridges (Alectoris rufa)

“…For this reason, the observed differences were most probably due to factors related to the WNV strain. Genetic changes, particularly those leading to amino acid substitutions, can modify the virulence of WNV strains, as well as other phenotypic traits such as host and/or mosquito competence [52][53][54][55]. The Morocco/2003 and Spain/2007 WNV strains differ in 13 amino acid positions; therefore, it is possible that one or several of these changes determined/modulated the virulence of both strains for the red-legged partridge [21].…”

Serological Evidence of West Nile Virus Infection Among Humans, Horses, and Pigeons in Saudi Arabia

“… 9 , 21 During the last two decades, WNV has become a leading infectious cause of human neuroinvasive disease. 4 This emphasizes that attention should be paid to diagnose and report such cases from Saudi Arabia.…”

“…3 Other mosquitoes such as Aedes species and Coquillettidia richiardii also serve as vectors for the transmission of WNV depending on the geographical location. 4 The virus thereafter replicates in the gut of the mosquito to the infectious levels and transmit to another bird during hematophagy. 3 In this complete cycle, the virus circulates in nature among birds and culex mosquitoes.…”

“… 3 Other mosquitoes such as Aedes species and Coquillettidia richiardii also serve as vectors for the transmission of WNV depending on the geographical location. 4 …”

Modulation of Serum Protein Electrophoretic Pattern and Leukocyte Population in Horses Vaccinated against West Nile Virus

“…Horses are not amplifying hosts as viraemia is low and transitory. Humoral immunity is a critical aspect of protection against flavivirus infection [ 9 , 10 ]. It is necessary for the initial containment and clearance of infection, as well as for subsequent protection against reinfection [ 11 , 12 , 13 ].…”