West Nile Virus: Epidemiology and Clinical Features of an Emerging Epidemic in the United States*

Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado 80522, USA.
Annual Review of Medicine (Impact Factor: 12.93). 02/2006; 57(1):181-94. DOI: 10.1146/
Source: PubMed

ABSTRACT West Nile virus (WNV) was first detected in North America in 1999 during an outbreak of encephalitis in New York City. Since then the virus has spread across North America and into Canada, Latin America, and the Caribbean. The largest epidemics of neuroinvasive WNV disease ever reported occurred in the United States in 2002 and 2003. This paper reviews new information on the epidemiology and clinical aspects of WNV disease derived from greatly expanded surveillance and research on WNV during the past six years.

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    • "WNV is maintained in nature in an enzootic transmission cycle between avian hosts and ornithophilic mosquito vectors, but it can infect multiple vertebrate species, including humans and horses (Martin-Acebes and Saiz, 2012). Although infections in humans are mainly asymptomatic, WNV can also induce a wide range of clinical symptoms that varies from a mild flu-like febrile illness termed WN fever to a neuroinvasive disease characterized by meningitis, encephalitis, or acute flaccid paralysis (Hayes and Gubler, 2006). "
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    ABSTRACT: West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for outbreaks of meningitis and encephalitis. Whereas the activation of autophagy in cells infected with other flaviviruses is well known, the interaction of WNV with the autophagic pathway still remains unclear and there are reports describing opposite findings obtained even analyzing the same viral strain. To clarify this controversy, we first analyzed the induction of autophagic features in cells infected with a panel of WNV strains. WNV was determined to induce autophagy in a strain dependent manner. We observed that all WNV strains or isolates analyzed, except for the WNV NY99 used, upregulated the autophagic pathway in infected cells. Interestingly, a variant derived from this WNV NY99 isolated from a persistently infected mouse increased LC3 modification and aggregation. Genome sequencing of this variant revealed only two non-synonymous nucleotide substitutions when compared to parental NY99 strain. These nucleotide substitutions introduced one amino acid replacement in NS4A and other in NS4B. Using genetically engineered viruses we showed that introduction of only one of these replacements was sufficient to upregulate the autophagic pathway. Thus, in this work we have shown that naturally occurring point mutations in the viral non-structural proteins NS4A and NS4B confer WNV with the ability to induce the hallmarks of autophagy such as LC3 modification and aggregation. Even more, the differences on the induction of an autophagic response observed among WNV variants in infected cells did not correlate with alterations on the activation of the unfolded protein response (UPR), suggesting an uncoupling of UPR and autophagy during flavivirus infection. The findings here reported could help to improve the knowledge of the cellular processes involved on flavivirus-host cell interactions and contribute to the design of effective strategies to combat these pathogens.
    Frontiers in Microbiology 01/2015; 5:797. DOI:10.3389/fmicb.2014.00797 · 3.99 Impact Factor
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    • "The intensity of WNV transmission to humans is dictated by seasonal feeding behavior and numbers of mosquitoes , as well as by local ecologic determinants of human exposure (Hayes and Gubler, 2006). WNV epidemics exhibit a seasonal variation in the United States, with most cases observed in the summer and early fall (June through October). "
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    ABSTRACT: West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are arthropod-borne flaviviruses that belong to the Japanese encephalitis virus antigenic complex. SLEV transmission is limited to North and South America, whereas WNV infection occurs on six continents. WNV is now the most common cause of epidemic viral meningoencephalitis in the United States and greater than 30 000 human cases have been reported since its emergence in New York City in 1999. Both viruses are maintained in the natural environment in a cycle between mosquitoes and birds. Human infection is an incidental, non-amplifying, dead-end occurrence in the lifecycle of these enzoonitic viruses and neither WNV nor SLEV is naturally transmitted from person to person. The majority of infections are asymptomatic (80%) and most clinical illness manifests as a self-limited, febrile, flu-like syndrome. However, a small percentage of individuals (<1%) develop neuroinvasive infection (meningitis, encephalitis, and myelitis) that can cause significant illness and death. There is currently no specific therapy of proven benefit or licensed human vaccine for either WNV or SLEV. This chapter reviews the epidemiology, virology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of WNV and SLEV, with particular emphasis on WNV, whose recent geographic expansion and global burden warrant in depth review.
    Handbook of Clinical Neurology 07/2014; 123C:433-447. DOI:10.1016/B978-0-444-53488-0.00020-1
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    • "West Nile virus (WNV) is a single-stranded positive polarity enveloped RNA virus and member of the Flavivirus genus of the Flaviviridae family. WNV is transmitted in a natural cycle between birds and mosquitoes [1] and causes morbidity and mortality in birds, horses, humans and some other vertebrate animals. In humans, WNV infections usually remains asymptomatic or causes a mild undifferentiated febrile illness called West Nile fever [2]. "
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    ABSTRACT: West Nile virus (WNV) is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI) covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime - boost regime) with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical). In parallel a heterologous boost with purified recombinant WNV envelope (E) protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8(+) specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.
    PLoS ONE 02/2014; 9(2):e87837. DOI:10.1371/journal.pone.0087837 · 3.23 Impact Factor
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