West Nile virus

Like most other flaviviruses, WNV is an enveloped virus with icosahedral symmetry.{{Cite journal|last1=Mukhopadhyay|first1=Suchetana|last2=Kim|first2=Bong-Suk|last3=Chipman|first3=Paul R.|last4=Rossmann|first4=Michael G.|last5=Kuhn|first5=Richard J.|date=2003-10-10|title=Structure of West Nile Virus|journal=Science|language=en|volume=302|issue=5643|page=248|doi=10.1126/science.1089316|issn=0036-8075|pmid=14551429|s2cid=23555900}} Electron microscope studies reveal a 45–50 nm virion covered with a relatively smooth protein shell; this structure is similar to the dengue fever virus, another Flavivirus. The protein shell is made of two structural proteins: the glycoprotein E and the small membrane protein M.{{Cite journal |last1=Kanai|first1=Ryuta|last2=Kar|first2=Kalipada|last3=Anthony|first3=Karen|last4=Gould|first4=L. Hannah|last5=Ledizet|first5=Michel|last6=Fikrig|first6=Erol|last7=Marasco|first7=Wayne A.|last8=Koski|first8=Raymond A.|last9=Modis|first9=Yorgo |date=2006-11-01 |title=Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes |journal=Journal of Virology|language=en|volume=80|issue=22|pages=11000–11008|doi=10.1128/jvi.01735-06|issn=0022-538X|pmid=16943291|pmc=1642136}} Protein E has numerous functions including receptor binding, viral attachment, and entry into the cell through membrane fusion.

The outer protein shell is covered by a host-derived lipid membrane, the viral envelope. The flavivirus lipid membrane has been found to contain cholesterol and phosphatidylserine, but other elements of the membrane have yet to be identified.{{Cite journal|last1=Meertens|first1=Laurent|last2=Carnec|first2=Xavier|last3=Lecoin|first3=Manuel Perera|last4=Ramdasi|first4=Rasika|last5=Guivel-Benhassine|first5=Florence|last6=Lew|first6=Erin|last7=Lemke|first7=Greg|last8=Schwartz|first8=Olivier|last9=Amara|first9=Ali|title=The TIM and TAM Families of Phosphatidylserine Receptors Mediate Dengue Virus Entry|journal=Cell Host & Microbe|volume=12|issue=4|pages=544–557|doi=10.1016/j.chom.2012.08.009|pmid=23084921|pmc=3572209|year=2012}}{{Cite journal|last1=Carro|first1=Ana C.|last2=Damonte|first2=Elsa B.|title=Requirement of cholesterol in the viral envelope for dengue virus infection|journal=Virus Research|volume=174|issue=1–2|pages=78–87|doi=10.1016/j.virusres.2013.03.005|pmid=23517753|year=2013|hdl=11336/85262|hdl-access=free}} The lipid membrane has many roles in viral infection, including acting as signaling molecules and enhancing entry into the cell.{{Cite journal|last1=Martín-Acebes|first1=Miguel A.|last2=Merino-Ramos|first2=Teresa|last3=Blázquez|first3=Ana-Belén|last4=Casas|first4=Josefina|last5=Escribano-Romero|first5=Estela|last6=Sobrino|first6=Francisco|last7=Saiz|first7=Juan-Carlos|date=2014-10-15|title=The Composition of West Nile Virus Lipid Envelope Unveils a Role of Sphingolipid Metabolism in Flavivirus Biogenesis|journal=Journal of Virology |language=en|volume=88|issue=20|pages=12041–12054|doi=10.1128/jvi.02061-14|issn=0022-538X|pmid=25122799|pmc=4178726}} Cholesterol, in particular, plays an integral part in WNV entering a host cell.{{Cite journal|last1=Medigeshi|first1=Guruprasad R.|last2=Hirsch|first2=Alec J.|last3=Streblow|first3=Daniel N.|last4=Nikolich-Zugich|first4=Janko|last5=Nelson|first5=Jay A.|date=2008-06-01|title=West Nile Virus Entry Requires Cholesterol-Rich Membrane Microdomains and Is Independent of αvβ3 Integrin|journal=Journal of Virology|language=en|volume=82|issue=11|pages=5212–5219|doi=10.1128/jvi.00008-08|issn=0022-538X|pmid=18385233|pmc=2395215}} The two viral envelope proteins, E and M, are inserted into the membrane.

The RNA genome is bound to capsid (C) proteins, which are 105 amino-acid residues long, to form the nucleocapsid. The capsid proteins are one of the first proteins created in an infected cell; the capsid protein is a structural protein whose main purpose is to package RNA into the developing viruses.{{Cite journal|last1=Hunt|first1=Tracey A.|last2=Urbanowski|first2=Matthew D.|last3=Kakani|first3=Kishore|last4=Law|first4=Lok-Man J.|last5=Brinton|first5=Margo A.|last6=Hobman|first6=Tom C.|date=2007-11-01|title=Interactions between the West Nile virus capsid protein and the host cell-encoded phosphatase inhibitor, I2PP2A|journal=Cellular Microbiology|language=en|volume=9|issue=11|pages=2756–2766|doi=10.1111/j.1462-5822.2007.01046.x|pmid=17868381|issn=1462-5822|doi-access=|s2cid=6224667 }} The capsid has been found to prevent apoptosis by affecting the Akt pathway.{{Cite journal|last1=Urbanowski|first1=Matt D.|last2=Hobman|first2=Tom C.|date=2013-01-15|title=The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism|journal=Journal of Virology|language=en|volume=87|issue=2|pages=872–881|doi=10.1128/jvi.02030-12|issn=0022-538X|pmid=23115297|pmc=3554064}}

File:Genome of the West Nile Virus.gif

WNV is a positive-sense, single-stranded RNA virus. Its genome is approximately 11,000 nucleotides long and is flanked by 5′ and 3′ non-coding stem loop structures.{{Cite journal|last1=Colpitts|first1=Tonya M.|last2=Conway|first2=Michael J.|last3=Montgomery|first3=Ruth R.|last4=Fikrig|first4=Erol|date=2012-10-01|title=West Nile Virus: Biology, Transmission, and Human Infection|journal=Clinical Microbiology Reviews|language=en|volume=25|issue=4|pages=635–648|doi=10.1128/cmr.00045-12|issn=0893-8512|pmid=23034323|pmc=3485754}} The coding region of the genome codes for three structural proteins and seven nonstructural (NS) proteins, proteins that are not incorporated into the structure of new viruses. The WNV genome is first translated into a polyprotein and later cleaved by virus and host proteases into separate proteins (i.e. NS1, C, E).{{Cite journal|last1=Chung|first1=Kyung Min|last2=Liszewski|first2=M. Kathryn|last3=Nybakken|first3=Grant|last4=Davis|first4=Alan E.|last5=Townsend|first5=R. Reid|last6=Fremont|first6=Daved H.|last7=Atkinson|first7=John P.|last8=Diamond|first8=Michael S.|date=2006-12-12|title=West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H|journal=Proceedings of the National Academy of Sciences|language=en|volume=103|issue=50|pages=19111–19116|doi=10.1073/pnas.0605668103|issn=0027-8424|pmid=17132743|pmc=1664712|doi-access=free}}

Structural proteins (C, prM/M, E) are capsid, precursor membrane proteins, and envelope proteins, respectively. The structural proteins are located at the 5′ end of the genome and are cleaved into mature proteins by both host and viral proteases.{{cn|date=October 2022}}

Nonstructural proteins consist of NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. These proteins mainly assist with viral replication or act as proteases. The nonstructural proteins are located near the 3′ end of the genome.

Once WNV has successfully entered the bloodstream of a host animal, the envelope protein, E, binds to attachment factors called glycosaminoglycans on the host cell. These attachment factors aid entry into the cell, however, binding to primary receptors is also necessary.{{Cite journal|last=Brinton|first=Margo A.|date=2002-10-01|title=The Molecular Biology of West Nile Virus: A New Invader of the Western Hemisphere|journal=Annual Review of Microbiology|volume=56|issue=1|pages=371–402|doi=10.1146/annurev.micro.56.012302.160654|pmid=12142476|issn=0066-4227}} Primary receptors include DC-SIGN, DC-SIGN-R, and the integrin α_vβ₃.{{Cite journal|last1=Samuel|first1=Melanie A.|last2=Diamond|first2=Michael S.|date=2006-10-01|title=Pathogenesis of West Nile Virus Infection: a Balance between Virulence, Innate and Adaptive Immunity, and Viral Evasion|journal=Journal of Virology|language=en|volume=80|issue=19|pages=9349–9360|doi=10.1128/jvi.01122-06|issn=0022-538X|pmid=16973541|pmc=1617273}} By binding to these primary receptors, WNV enters the cell through clathrin-mediated endocytosis.{{Cite journal|last1=Vancini|first1=Ricardo|last2=Kramer|first2=Laura D.|last3=Ribeiro|first3=Mariana|last4=Hernandez|first4=Raquel|last5=Brown|first5=Dennis|title=Flavivirus infection from mosquitoes in vitro reveals cell entry at the plasma membrane|journal=Virology|volume=435|issue=2|pages=406–414|doi=10.1016/j.virol.2012.10.013|pmid=23099205|year=2013|doi-access=free}} As a result of endocytosis, WNV enters the cell within an endosome.{{cn|date=October 2022}}

The acidity of the endosome catalyzes the fusion of the endosomal and viral membranes, allowing the genome to be released into the cytoplasm.{{Cite journal|last1=Mukhopadhyay|first1=Suchetana|last2=Kuhn|first2=Richard J.|last3=Rossmann|first3=Michael G.|title=A structural perspective of the flavivirus life cycle|journal=Nature Reviews Microbiology|volume=3|issue=1|pages=13–22|doi=10.1038/nrmicro1067|pmid=15608696|year=2005|s2cid=4150641}} Translation of the positive-sense single-stranded RNA occurs at the endoplasmic reticulum; the RNA is translated into a polyprotein which is then cleaved by both host and viral proteases NS2B-NS3 to produce mature proteins.{{Cite journal|last1=Suthar|first1=Mehul S.|last2=Diamond|first2=Michael S.|last3=Gale|first3=Michael Jr.|title=West Nile virus infection and immunity|journal=Nature Reviews Microbiology|volume=11|issue=2|pages=115–128|doi=10.1038/nrmicro2950|pmid=23321534|year=2013|s2cid=1013677}}

In order to replicate its genome, NS5, a RNA polymerase, forms a replication complex with other nonstructural proteins to produce an intermediary negative-sense single-stranded RNA; the negative-sense strand serves as a template for synthesis of the final positive-sense RNA. Once the positive-sense RNA has been synthesized, the capsid protein, C, encloses the RNA strands into immature virions. The rest of the virus is assembled along the endoplasmic reticulum and through the Golgi apparatus, and results in non-infectious immature virions. The E protein is then glycosylated and prM is cleaved by furin, a host cell protease, into the M protein, thereby producing an infectious mature virion. The mature viruses are then secreted out of the cell.{{cn|date=October 2022}}

File:Phylogenetic tree of West Nile viruses.gif of West Nile viruses based on sequencing of the envelope gene during complete genome sequencing of the virus{{cite journal |vauthors=Lanciotti RS, Ebel GD, Deubel V, etal |title=Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East |journal=Virology |volume=298 |issue=1 |pages=96–105 |date=June 2002 |pmid=12093177 |doi=10.1006/viro.2002.1449 |s2cid=17275232 |doi-access=free }}]]

WNV is one of the Japanese encephalitis antigenic serocomplex of viruses, together with Japanese encephalitis virus, Murray Valley encephalitis virus, Saint Louis encephalitis virus and some other flaviviruses.{{cite journal | pmc=3337329 | pmid=22309667 | doi=10.1586/erv.11.180 | volume=11 | issue=2 | title=Feasibility of cross-protective vaccination against flaviviruses of the Japanese encephalitis serocomplex | year=2012 | journal=Expert Rev Vaccines | pages=177–87 |vauthors=Lobigs M, Diamond MS }} Studies of phylogenetic lineages have determined that WNV emerged as a distinct virus around 1000 years ago.{{cite journal |vauthors=Galli M, Bernini F, Zehender G |title=Alexander the Great and West Nile virus encephalitis |journal=Emerging Infect. Dis. |volume=10 |issue=7 |pages=1330–2; author reply 1332–3 |date=July 2004 |pmid=15338540 |doi=10.3201/eid1007.040396 |doi-access= }} This initial virus developed into two distinct lineages. Lineage 1 and its multiple profiles is the source of the epidemic transmission in Africa and throughout the world. Lineage 2 was considered an African zoonosis. However, in 2008, lineage 2, previously only seen in horses in sub-Saharan Africa and Madagascar, began to appear in horses in Europe, where the first known outbreak affected 18 animals in Hungary.{{cite journal|url=http://www.thehorse.com/ViewArticle.aspx?ID=15779|title=Different West Nile Virus Genetic Lineage Evolving?|author=West, Christy|journal=The Horse|date=2010-02-08|access-date=2010-02-10|url-status=live|archive-url=https://web.archive.org/web/20100217033448/http://www.thehorse.com/ViewArticle.aspx?ID=15779|archive-date=2010-02-17}} From statements by Orsolya Kutasi, DVM, of the Szent Istvan University, Hungary at the 2009 American Association of Equine Practitioners Convention, December 5–9, 2009. Lineage 1 West Nile virus was detected in South Africa in 2010 in a mare and her aborted fetus; previously, only lineage 2 West Nile virus had been detected in horses and humans in South Africa.{{cite journal |vauthors=Venter M, Human S, van Niekerk S, Williams J, van Eeden C, Freeman F |title=Fatal neurologic disease and abortion in mare infected with lineage 1 West Nile virus, South Africa |journal=Emerging Infect. Dis. |volume=17 |issue=8 |pages=1534–6 |date=August 2011 |pmid=21801644 |pmc=3381566 |doi=10.3201/eid1708.101794 }} Kunjin virus is a subtype of West Nile virus endemic to Oceania. A 2007 fatal case in a killer whale in Texas broadened the known host range of West Nile virus to include cetaceans.{{cite journal |vauthors=St Leger J, Wu G, Anderson M, Dalton L, Nilson E, Wang D |title=West Nile virus infection in killer whale, Texas, USA, 2007 |journal=Emerging Infect. Dis. |volume=17 |issue=8 |pages=1531–3 |year=2011 |pmid=21801643 |pmc=3381582 |doi=10.3201/eid1708.101979 }}

Since the first North American cases in 1999, the virus has been reported throughout the United States, Canada, Mexico, the Caribbean, and Central America. There have been human cases and equine cases, and many birds are infected. The Barbary macaque, Macaca sylvanus, was the first nonhuman primate to contract WNV.Hogan, C. Michael (2008). [http://globaltwitcher.auderis.se/artspec_information.asp?thingid=31757 Barbary Macaque: Macaca sylvanus, GlobalTwitcher.com] {{webarchive|url=https://web.archive.org/web/20090831095518/http://globaltwitcher.auderis.se/artspec_information.asp?thingid=31757 |date=2009-08-31 }} Both the American and Israeli strains are marked by high mortality rates in infected avian populations; the presence of dead birds—especially Corvidae—can be an early indicator of the arrival of the virus.{{cn|date=October 2022}}

File:Pipiens feeding.jpg mosquitoes are a vector for WNV.]]

The natural hosts for WNV are birds and mosquitoes. Over 300 different species of bird have been shown to be infected with the virus.{{cite web |url=https://www.cdc.gov/westnile/resources/pdfs/BirdSpecies1999-2016.pdf |title=Species of dead birds in which West Nile virus has been detected, United States, 1999–2016 |publisher=CDC |access-date=28 March 2019 }} Some birds, including the American crow (Corvus brachyrhynchos), blue jay (Cyanocitta cristata) and greater sage-grouse (Centrocercus urophasianus), are killed by the infection, but others survive.{{cite journal |title=West Nile Virus Infection in American Robins: New Insights on Dose Response |author=Kaci K. VanDalen |author2=Jeffrey S. Hall |author3=Larry Clark |author4=Robert G. McLean |author5=Cynthia Smeraski |journal=PLOS One |year=2013 |volume=8 |issue=7 |page=e68537 |doi=10.1371/journal.pone.0068537 |pmid=23844218|pmc=3699668 |bibcode=2013PLoSO...868537V |doi-access=free }} The American robin (Turdus migratorius) and house sparrow (Passer domesticus) are thought to be among the most important reservoir species in N. American and European cities.{{cite journal |title=Pathology and tissue tropism of natural West Nile virus infection in birds: a review |author=Virginia Gamino |author2=Ursula Höfle |journal=Veterinary Research |year=2013 |volume=44 |issue=1 |page=39 |doi=10.1186/1297-9716-44-39|pmid=23731695 |pmc=3686667 |doi-access=free }} Brown thrashers (Toxostoma rufum), gray catbirds (Dumetella carolinensis), northern cardinals (Cardinalis cardinalis), northern mockingbirds (Mimus polyglottos), wood thrushes (Hylocichla mustelina) and the dove family are among the other common N. American birds in which high levels of antibodies against WNV have been found.

File:Culex Mosquito and Micrograph of West Nile Virus Particles.jpg

WNV has been demonstrated in a large number of mosquito species, but the most significant for viral transmission are Culex species that feed on birds, including Culex pipiens, C. restuans, C. salinarius, C. quinquefasciatus, C. nigripalpus, C. erraticus and C. tarsalis.{{cite journal |author=Kilpatrick, AM |author2=SL LaDeau |author3=PP Marra | title= Ecology of West Nile virus transmission and its impact on birds in the western hemisphere |journal= The Auk |volume= 124 |issue= 4 |year=2007 | pages=1121–36 |doi=10.1642/0004-8038(2007)124[1121:EOWNVT]2.0.CO;2 |s2cid=13796761 |url= https://repository.si.edu/bitstream/handle/10088/35181/NZP_Marra_2007-ECOLOGY_OF_WEST_NILE_VIRUS_TRANSMISSION_AND_ITS_IMPACT_ON_BIRDS_IN_THE_WESTERN_HEMISPHERE.pdf}} Experimental infection has also been demonstrated with soft tick vectors, but is unlikely to be important in natural transmission.{{cite journal |last1=Lawrie |first1=Charles |last2=Uzcátegui |first2=Nathalie |last3=Gould |first3=Ernest |last4=Nuttall |first4=Patricia |title=Ixodid and Argasid Tick Species and West Nile Virus |journal= Emerging Infectious Diseases|volume=10 |issue=4 |pages=653–657 |date=April 2004 |doi=10.3201/eid1004.030517 |pmid=15200855 |pmc=3323096 }}

WNV has a broad host range, and is also known to be able to infect at least 30 mammalian species, including humans, some non-human primates,{{cite journal |url=https://wwwnc.cdc.gov/eid/article/9/11/pdfs/03-0226.pdf |title=West Nile Virus Infection in Nonhuman Primate Breeding Colony, Concurrent with Human Epidemic, Southern Louisiana |author=Marion S. Ratterree |author2=Amelia P.A. Travassos da Rosa |author3=Rudolf P. Bohm Jr. |display-authors=etal |journal=Emerging Infectious Diseases |year=2003 |volume=9 |issue=11 |pages=1388–94 |doi=10.3201/eid0911.030226 |pmid=14718080 }} horses, dogs and cats.{{cite web |url=https://www.who.int/news-room/fact-sheets/detail/west-nile-virus |title=West Nile virus |publisher=World Health Organization |date=3 October 2017 |access-date=28 March 2019 }}{{cite web |title=Vertebrate Ecology |date=30 April 2009 |work=West Nile Virus |publisher=Division of Vector-Borne Diseases, CDC |url=https://www.cdc.gov/ncidod/dvbid/westnile/birds&mammals.htm |url-status=live |archive-url=https://web.archive.org/web/20130301003126/http://www.cdc.gov/ncidod/dvbid/westnile/birds%26mammals.htm |archive-date=1 March 2013 }}{{cite journal |author=Kilpatrick, AM |author2=P Daszak |author3=MJ Jones |author4=PP Marra |author5=LD Kramer |year=2006|title=Host heterogeneity dominates West Nile virus transmission|journal=Proceedings of the Royal Society B: Biological Sciences|volume=273|issue=1599|pages=2327–2333|doi=10.1098/rspb.2006.3575|pmc=1636093|pmid=16928635}} Some infected humans and horses experience disease but dogs and cats rarely show symptoms. Reptiles and amphibians can also be infected, including some species of crocodiles, alligators, snakes, lizards and frogs.{{cite journal |title=West Nile Virus and Wildlife |author=Peter P. Marra |author2=Sean Griffing |author3=Carolee Caffrey |display-authors=etal |journal=BioScience |year=2004 |volume=54 |issue=5 |pages=393–402 |doi=10.1641/0006-3568(2004)054[0393:WNVAW]2.0.CO;2 |doi-access=free }}{{cite journal |title=West Nile Virus Infection in Crocodiles |author=Amir Steinman |author2=Caroline Banet-Noach |author3=Shlomit Tal |display-authors=etal |journal=Emerging Infectious Diseases |year=2003 |volume=9 |issue=7 |pages=887–89 |doi=10.3201/eid0907.020816 |pmid=12899140 |pmc=3023443 }}{{cite journal |title=Wild snakes harbor West Nile virus |author=C. R. Dahlina |author2=D. F. Hughes |author3=W. E. Meshaka Jr. |author4=C. Coleman |author5=J. D. Henning |journal=One Health |year=2016 |volume=2 |pages=136–38 |doi=10.1016/j.onehlt.2016.09.003 |pmid=28616487 |pmc=5441359 }}{{cite journal |title=Viruses in reptiles |author=Ellen Ariel |journal=Veterinary Research |year=2011 |volume=42 |issue=1 |page=100 |doi=10.1186/1297-9716-42-100 |pmid=21933449 |pmc=3188478 |doi-access=free }} Mammals are considered incidental or dead-end hosts for the virus: they do not usually develop a high enough level of virus in the blood (viremia) to infect another mosquito feeding on them and carry on the transmission cycle; some birds are also dead-end hosts.

In the normal rural or enzootic transmission cycle, the virus alternates between the bird reservoir and the mosquito vector. It can also be transmitted between birds via direct contact, by eating an infected bird carcass or by drinking infected water. Vertical transmission between female and offspring is possible in mosquitoes, and might potentially be important in overwintering.{{cite journal |vauthors=Goddard LB, Roth AE, Reisen WK, Scott TW |title=Vertical transmission of West Nile Virus by three California Culex (Diptera: Culicidae) species |journal=J. Med. Entomol. |volume=40 |issue=6 |pages=743–6 |date=November 2003 |pmid=14765647 |doi=10.1603/0022-2585-40.6.743 |doi-access=free }}{{cite journal | first = LM | last = Bugbee |author2=Forte LR |date=September 2004 | title = The discovery of West Nile virus in overwintering Culex pipiens (Diptera: Culicidae) mosquitoes in Lehigh County, Pennsylvania|journal = Journal of the American Mosquito Control Association | volume = 20 | issue = 3 | pages = 326–7 | pmid = 15532939}} In the urban or spillover cycle, infected mosquitoes that have fed on infected birds transmit the virus to humans. This requires mosquito species that bite both birds and humans, which are termed bridge vectors.{{cite web|date=19 October 2017|title=General Questions About West Nile Virus|url=https://www.cdc.gov/westnile/faq/genQuestions.html|url-status=live|archive-url=https://web.archive.org/web/20171026111330/https://www.cdc.gov/westnile/faq/genQuestions.html|archive-date=26 October 2017|access-date=26 October 2017|website=www.cdc.gov|language=en-us}}{{cite journal |title=Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases |author=Scott C. Weaver |author2=Caroline Charlier |author3=Nikos Vasilakis |author4=Marc Lecuit |journal=Annual Review of Medicine |year=2018 |volume=69 |pages=395–408 |doi=10.1146/annurev-med-050715-105122 |pmid = 28846489|pmc = 6343128}} The virus can also rarely be spread through blood transfusions, organ transplants, or from mother to baby during pregnancy, delivery, or breastfeeding. Unlike in birds, it does not otherwise spread directly between people.{{cite web|title=West Nile virus|url=https://www.who.int/mediacentre/factsheets/fs354/en/|website=World Health Organization|access-date=28 October 2017|date=July 2011|url-status=live|archive-url=https://web.archive.org/web/20171018044431/http://www.who.int/mediacentre/factsheets/fs354/en/|archive-date=18 October 2017}}

Experimental studies have shown that American alligators (Alligator mississippiensis) can become infected with WNV and develop viremia levels sufficient to infect mosquitoes, suggesting a role as amplifying hosts.Byas AD, Gallichotte EN, Hartwig AE, et al. American alligators are capable of West Nile virus amplification, mosquito infection and transmission. Virology. 2022;568:49–55. https://doi.org/10.1016/j.virol.2022.01.009 The study also demonstrated that infected mosquitoes can transmit the virus to alligators, and that alligators can subsequently infect mosquitoes through bloodfeeding. These findings indicate a possible contribution of alligators to local WNV transmission cycles, particularly in regions where they are densely farmed or cohabitate with mosquito populations.

{{Excerpt|West Nile fever}}

Horses are considered highly susceptible to West Nile virus (WNV) infection. Although many equine infections are asymptomatic, approximately 10–40% of infected horses may develop clinical signs, which can result in severe neurological disease..Ronca SE, Ruff JC, Murray KO. A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease? PLoS Negl Trop Dis. 2021;15(5):e0009190. https://doi.org/10.1371/journal.pntd.0009190 Clinical signs in symptomatic cases include ataxia, weakness, fever, recumbency, and, in some instances, death.Ronca SE, Ruff JC, Murray KO. A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease? PLoS Negl Trop Dis. 2021;15(5):e0009190. https://doi.org/10.1371/journal.pntd.0009190 The case fatality rate among symptomatic horses has been estimated at 30–40%, although outcomes improve significantly with supportive care and early intervention.

Comparative studies have highlighted significant similarities between WNV disease in horses and humans, including overlapping geographic distribution, shared environmental risk factors, and analogous clinical manifestations. These parallels suggest that horses can serve as effective sentinel species for monitoring WNV activity and enhancing syndromic surveillance efforts.Schwarz ER, Long MT. Comparison of West Nile Virus Disease in Humans and Horses: Exploiting Similarities for Enhancing Syndromic Surveillance. Viruses. 2023;15(6):1230. https://doi.org/10.3390/v15061230

Horses are infected by the bite of mosquitoes that have acquired the virus from birds. The disease is not spread directly between horses or from horses to humans.Naveed A, Eertink LG, Wang D, Li F. Lessons Learned from West Nile Virus Infection: Vaccinations in Equines and Their Implications for One Health Approaches. Viruses. 2024;16(5):781. https://doi.org/10.3390/v16050781

Since the introduction of equine WNV vaccines in the United States in 2002, there has been a significant decline in the number of WNV cases among vaccinated horse populations. However, sporadic cases continue to occur, primarily in unvaccinated or under-vaccinated equines. This underscores the importance of maintaining high vaccination coverage and implementing comprehensive mosquito control measures to prevent outbreaks.Naveed A, Eertink LG, Wang D, Li F. Lessons Learned from West Nile Virus Infection: Vaccinations in Equines and Their Implications for One Health Approaches. Viruses. 2024;16(5):781. https://doi.org/10.3390/v16050781

The successful deployment of WNV vaccines in equine populations offers valuable insights for human vaccine development. Understanding the immune responses elicited by these vaccines in horses can inform strategies aimed at developing effective human vaccines, aligning with the One Health approach that emphasizes the interconnectedness of human, animal, and environmental health.

According to the Centers for Disease Control and Prevention, infection with West Nile Virus is seasonal in temperate zones. Climates that are temperate, such as those in the United States and Europe, see peak season from July to October. Peak season changes depending on geographic region and warmer and humid climates can see longer peak seasons.{{Cite journal|last1=Hayes|first1=Edward B.|last2=Komar|first2=Nicholas|last3=Nasci|first3=Roger S.|last4=Montgomery|first4=Susan P.|last5=O'Leary|first5=Daniel R.|last6=Campbell|first6=Grant L.|date= August 2005 |title=Epidemiology and Transmission Dynamics of West Nile Virus Disease|journal=Emerging Infectious Diseases|volume=11|issue=8|pages=1167–1173|doi=10.3201/eid1108.050289a|pmid=16102302|pmc=3320478|issn=1080-6040}} All ages are equally likely to be infected but there is a higher amount of death and neuroinvasive West Nile Virus in people 60–89 years old. People of older age are more likely to have adverse effects.{{cn|date=October 2022}}

There are several modes of transmission, but the most common cause of infection in humans is by being bitten by an infected mosquito. Other modes of transmission include blood transfusion, organ transplantation, breast-feeding, transplacental transmission, and laboratory acquisition. These alternative modes of transmission are extremely rare.{{Cite journal|last=Sampathkumar|first=Priya | date= September 2003 |title=West Nile Virus: Epidemiology, Clinical Presentation, Diagnosis, and Prevention|journal=Mayo Clinic Proceedings|volume=78|issue=9|pages=1137–1144|doi=10.4065/78.9.1137|pmid=12962168|pmc=7125680 |issn=0025-6196|doi-access=free}}

Prevention efforts against WNV mainly focus on preventing human contact with and being bitten by infected mosquitoes. This is twofold, first by personal protective actions and second by mosquito-control actions. When a person is in an area that has WNV, it is important to avoid outdoor activity, and if they go outside they should use a mosquito repellent with DEET. A person can also wear clothing that covers more skin, such as long sleeves and pants. Mosquito control can be done at the community level and include surveillance programs and control programs including pesticides and reducing mosquito habitats. This includes draining standing water. Surveillance systems in birds is particularly useful.{{Cite journal|date=2001-11-14|title=West Nile Virus Activity—United States, October 17-23, 2001|journal=JAMA|volume=286|issue=18|page=2232|doi=10.1001/jama.286.18.2232-jwr10138-2-1|issn=0098-7484|doi-access=}} If dead birds are found in a neighborhood, the event should be reported to local authorities. This may help health departments do surveillance and determine if the birds are infected with West Nile Virus.{{Cite journal|last1=McCormick|first1=Sabrina|last2=Whitney|first2=Kristoffer|date=2012-12-20|title=The making of public health emergencies: West Nile virus in New York City|journal=Sociology of Health & Illness|volume=35|issue=2|pages=268–279|doi=10.1111/1467-9566.12002|pmid=23278188|issn=0141-9889|doi-access=free}}

Despite the commercial availability of four veterinary vaccines for horses, no human vaccine has progressed beyond phase II clinical trials.{{Cite journal|last1=Seino|first1=K. K.|last2=Long|first2=M. T.|last3=Gibbs|first3=E. P. J.|last4=Bowen|first4=R. A.|last5=Beachboard|first5=S. E.|last6=Humphrey|first6=P. P.|last7=Dixon|first7=M. A.|last8=Bourgeois|first8=M. A.|date=2007-11-01|title=Comparative Efficacies of Three Commercially Available Vaccines against West Nile Virus (WNV) in a Short-Duration Challenge Trial Involving an Equine WNV Encephalitis Model|journal=Clinical and Vaccine Immunology|language=en|volume=14|issue=11|pages=1465–1471|doi=10.1128/CVI.00249-07|issn=1556-6811|pmid=17687109|pmc=2168174}}{{Cite journal|last1=Kaiser|first1=Jaclyn A.|last2=Barrett|first2=Alan D.T.|date=2019-09-05|title=Twenty Years of Progress Toward West Nile Virus Vaccine Development|journal=Viruses|volume=11|issue=9|page=823|doi=10.3390/v11090823|issn=1999-4915|pmc=6784102|pmid=31491885|doi-access=free}} Efforts have been made to produce a vaccine for human use and several candidates have been produced but none are licensed to use. The best method to reduce the risk of infections is avoiding mosquito bites. This may be done by eliminating standing pools of water, such as in old tires, buckets, gutters, and swimming pools. Mosquito repellent, window screens, mosquito nets, and avoiding areas where mosquitoes occur may also be useful.

File:Global distribution of West Nile virus-CDC.gif{{Further|Climate change and infectious diseases}}

Like other tropical diseases which are expected to have increased spread due to climate change, there is concern that changing weather conditions will increase West Nile Virus spread. Climate change will affect disease rates, ranges, and seasonality and affects the distribution of West Nile Virus.{{Cite journal|last=Paz|first=Shlomit|date=2015-04-05|title=Climate change impacts on West Nile virus transmission in a global context|journal=Philosophical Transactions of the Royal Society B: Biological Sciences|language=en|volume=370|issue=1665|page=20130561|doi=10.1098/rstb.2013.0561|issn=0962-8436|pmc=4342965|pmid=25688020}}

Projected changes in flood frequency and severity can bring new challenges in flood risk management, allowing for increased mosquito populations in urban areas.{{Cite report|title=Appendix 6: Topics for Consideration in Future Assessments. Climate Change Impacts in the United States: The Third National Climate Assessment|date=2014|publisher=U.S. Global Change Research Program|doi=10.7930/j06h4fbf|work=National Climate Assessment}} Weather conditions affected by climate change including temperature, precipitation and wind may affect the survival and reproduction rates of mosquitoes, suitable habitats, distribution, and abundance. Ambient temperatures drive mosquito replication rates and transmission of WNV by affecting the peak season of mosquitoes and geographic variations. For example, increased temperatures can affect the rate of virus replication, speed up the virus evolution rate, and viral transmission efficiency. Furthermore, higher winter temperatures and warmer spring may lead to larger summer mosquito populations, increasing the risk for WNV. Similarly, rainfall may also drive mosquito replication rates and affect the seasonality and geographic variations of the virus. Studies show an association between heavy precipitation and higher incidence of reported WNV. Likewise, wind is another environmental factor that serves as a dispersal mechanism for mosquitoes.

Mosquitoes have extremely wide environmental tolerances and a nearly ubiquitous geographical distribution, being present on all major land masses except Antarctica and Iceland. Nevertheless, changes in climate and land use on ecological timescales can variously expand or fragment their distribution patterns, raising consequent concerns for human health.{{Cite journal|last1=Andersen|first1=Louise K.|last2=Davis|first2=Mark D. P.|date=2016-10-01|title=Climate change and the epidemiology of selected tick-borne and mosquito-borne diseases: update from the International Society of Dermatology Climate Change Task Force|journal=International Journal of Dermatology|volume=56|issue=3|pages=252–259|doi=10.1111/ijd.13438|pmid=27696381|s2cid=23187115|issn=0011-9059}}

{{Portal|Viruses}}

• West Nile fever
• West Nile virus in the United States

{{Reflist}}

• [https://www.invasivespeciesinfo.gov/profile/west-nile-virus Species Profile - West Nile Virus], National Invasive Species Information Center, United States National Agricultural Library. Lists general information and resources for West Nile Virus

{{Scholia|topic}}

{{Zoonotic viral diseases}}

{{Taxonbar|from=Q158856}}

{{Authority control}}

{{DEFAULTSORT:West Nile Virus}}

Category:Flaviviruses