West Nile virus (WNV) is an emerging neurotropic flavivirus that naturally circulates between mosquitoes and birds. However, WNV has a broad host range and can be transmitted from mosquitoes to several mammalian species, including humans, through infected saliva during a blood meal. Although WNV infections are mostly asymptomatic, 20% to 30% of cases are symptomatic and can occasionally lead to severe symptoms, including fatal meningitis or encephalitis. Over the past decades, WNV-carrying mosquitoes have become increasingly widespread across new regions, including North America and Europe, which constitutes a public health concern. Nevertheless, mosquito and human innate immune defenses can detect WNV infection and induce the expression of antiviral effectors, so-called viral restriction factors, to control viral propagation. Conversely, WNV has developed countermeasures to escape these host defenses, thus establishing a constant arms race between the virus and its hosts. Our review intends to cover most of the current knowledge on viral restriction factors as well as WNV evasion strategies in mosquito and human cells in order to bring an updated overview on WNV–host interactions.
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