WNV is an enveloped, spherical, single-stranded RNA arbovirus of the family Flaviviridae. Other flaviviruses include yellow fever, dengue, and St. Louis encephalitis viruses.  WNV primarily circulates between infected birds (>130 different species) and the insects that bite them, usually female mosquitoes. The infected mosquitoes transmit the virus when they bite other animals (e.g., horses) or people.  WNV can also rarely be transmitted by transfusion of infected blood, transplantation of infected organs, and transplacentally from mother to fetus. Other uncommon routes of transmission are needlestick injuries involving infected blood, exposure of the conjunctiva to infected blood, dialysis, or breastfeeding.     
The typical incubation period is between 3 and 5 days and may last up to 14 days. The incubation period can last even longer (up to 21 days) in immunocompromised patients.  After the mosquito injects virus-laden saliva into the patient, the virus probably replicates in dendritic cells at the bite site and then spreads to lymph nodes and the bloodstream. Alternatively, the virus may enter the body through exposure to infected blood or organ transplants. The pathogenesis of severe infection is not well understood. In neuroinvasive disease, the virus crosses the blood-brain barrier into the CNS and directly infects neurons, especially in the deep nuclei and gray matter of the brain, brain stem, and spinal cord, causing neuronal inflammation, destruction, and death. The immune response to the virus also may contribute to neuronal damage. Demyelination and gliosis may occur in prolonged disease.