Abstract
Vector-borne diseases, including arboviruses, pose a serious threat to public health worldwide. Arboviruses of the flavivirus genus, such as Zika virus (ZIKV), dengue virus, yellow fever virus (YFV), and West Nile virus (WNV), are transmitted to humans from insect vectors and can cause serious disease. In 2017, over 2,000 reported cases of WNV virus infection occurred in the United States, with two-thirds of cases classified as neuroinvasive. WNV transmission cycles through two different animal populations: birds and mosquitoes. Mammals, particularly humans and horses, can become infected through mosquito bites and represent dead-end hosts of WNV infection. Because WNV can infect diverse species, research on this arbovirus has investigated the host response in mosquitoes, birds, humans, and horses. With the growing geographical range of the WNV mosquito vector and increased human exposure, improved surveillance and treatment of the infection will enhance public health in areas where WNV is endemic. In this review, we survey the bionomics of mosquito species involved in Nearctic WNV transmission. Subsequently, we describe the known immune response pathways that counter WNV infection in insects, birds, and mammals, as well as the mechanisms known to curb viral infection. Moreover, we discuss the bacterium Wolbachia and its involvement in reducing flavivirus titer in insects. Finally, we highlight the similarities of the known immune pathways and identify potential targets for future studies aimed at improving antiviral therapeutic and vaccination design.
Highlights
West Nile virus (WNV) belongs to the flavivirus genus, which includes dengue virus (DENV), yellow fever virus (YFV), and Zika virus (ZIKV)
We discuss mosquito populations in North America with particular attention to species that bridge WNV infection to humans, and survey the innate immune response pathways of the animals commonly infected with WNV: mosquitoes, birds, horses, and humans
While the adaptive immune response is important for mammalian survival to WNV, this review focuses on innate pathways and rapid immune activation during WNV infection
Summary
West Nile virus (WNV) belongs to the flavivirus genus, which includes dengue virus (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). WNV is endemic to the United States (U.S.) and Canada, Africa, Europe, the Middle East, and West Asia (WHO, 2011).WNV has a singlestranded positive-sense RNA genome encoding approximately 11,000 nucleotides It is translated as a polyprotein and processed into 3 structural and 7 nonstructural viral proteins (reviewed in Brinton, 2013). West Nile Virus Immune Responses infection (Figure 1E), or can bridge the infection to mammals, most commonly humans and horses (Figure 1F). It is at this interface that public health becomes a concern. We discuss mosquito populations in North America with particular attention to species that bridge WNV infection to humans, and survey the innate immune response pathways of the animals commonly infected with WNV: mosquitoes, birds, horses, and humans. We identify new areas for investigation, especially those focused on vaccine development and disease therapeutics
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