West Nile Virus: Immunity and Pathogenesis

Abstract

West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that is maintained in an enzootic cycle between mosquitoes and birds, but can also infect and cause disease in horses and humans. WNV is endemic in parts of Africa, Europe, the Middle East, and Asia, and since 1999 has spread to North America, Mexico, South America, and the Caribbean. WNV infects the central nervous system (CNS) and can cause severe disease in a small minority of infected humans, mostly immunocompromised or the elderly. This review discusses some of the mechanisms by which the immune system can limit dissemination of WNV infection and elaborates on the mechanisms involved in pathogenesis. Reasons for susceptibility to WNV-associated neuroinvasive disease in less than 1% of cases remain unexplained, but one favored hypothesis is that the involvement of the CNS is associated with a weak immune response allowing robust WNV replication in the periphery and spread of the virus to the CNS.

Frequency of West Nile Virus Infection in Iranian Blood Donors

“…It is endemic in parts of Africa, Asia, and the Middle East, parts of Europe, the America and Caribbean Islands [1].…”

“…West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that is maintained in an enzootic cycle between mosquitoes and birds, but can also infect and cause disease in horses and humans [1].…”

Neuroinvasive Arboviral Disease in the United States: 2003 to 2012

“…22 Although the reasons for higher incidence and severity of West Nile virus neuroinvasive disease in older age groups are not fully understood, possible explanations include changes in innate and adaptive immune function resulting in increased duration and magnitude of viremia or enhanced viral entry into the central nervous system due to disruption of the cerebral endothelium from conditions such as hypertension and cerebrovascular disease. 23,24 La Crosse virus, an orthobunyavirus, is transmitted by Aedes triseriatus, a mosquito that lives and breeds in the water holes of trees and other vessels, with gray squirrels and chipmunks serving as primary amplifying hosts. 12 Accordingly, La Crosse virus has been reported in distinct geographic regions with wooded areas that support its transmission cycle.…”

“…States with the highest annual incidence were in the North Central and Mountain regions, including South Dakota (10.36 per million children), Wyoming (5.91), North Dakota (5.34), and Nebraska (5.23). Seven states reported more than half of all cases: Texas (77 cases), California (49), Louisiana (34), Colorado (32), Arizona (29), Nebraska (24), and South Dakota (21). In the 2012 resurgence of West Nile virus, most cases occurred in the south, with 27 (33%) of the 83 reported cases of pediatric neuroinvasive disease occurring in Texas.…”

West Nile Virus: Basic Principles, Replication Mechanism, Immune Response and Important Genetic Determinants of Virulence

“…However, the virus can also spread between individuals by blood transfusion and organ transplantation and few reports have also proposed the transmission from mother to newborn via the intrauterine route or via breast-feeding [75][76][77]. Most human infections remain asymptomatic, West Nile fever (a mild flu like fever) develops in approximately 20 to 30% of infected persons and West Nile neuroinvasive disease in <1% [78], characterized by encephalitis, meningitis, acute flaccid paralysis and even long-term neurological sequeale [79]. Nonetheless, horses and humans develop viremia levels of low magnitude (<10 5 PFU/ml) and short duration insufficient to infect mosquitoes and thus do not serve as amplifying hosts for WNV in nature [80].…”