West Nile virus: Epidemiology and clinical features of an emerging epidemic in the United States
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.
- SourceAvailable from: Miguel A. Martín-Acebes
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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). "
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 · 3.94 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). "
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 01/2014; 123C:433-447. DOI:10.1016/B978-0-444-53488-0.00020-1
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- "Humans are thought to be only incidental hosts in the transmission cycle of WNV in which birds serve as the amplifying hosts of the virus and Culex mosquitoes serve as the primary vector . Although the majority of cases of WNV are asymptomatic, approximately 20% of infections result in symptomatic West Nile fever or neuroinvasive disease (WNND) manifesting as encephalitis, meningitis, or flaccid paralysis resembling poliomyelitis   . The first outbreak of WNV in the Western Hemisphere occurred in New York in 1999, and since that time, WNV has become the leading vector-borne cause of viral encephalitis in the United States  . "
ABSTRACT: WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age. There is no licensed treatment for WNND, nor is there any licensed vaccine for humans for the prevention of WNV infection. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 candidate vaccine rDEN4Δ30. The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the resultant virus was designated rWN/DEN4Δ30. The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18-50 years in two separate studies, both of which are reported here. The first study evaluated 10(3) or 10(4)PFU of the vaccine given as a single dose; the second study evaluated 10(5)PFU of the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (10(3)PFU), 75% (10(4)PFU), and 55% (10(5)PFU) of subjects after a single dose. A second 10(5)PFU dose of rWN/DEN4Δ30 given 6 months after the first dose increased the seroconversion rate 89%. Based on the encouraging results from these studies, further evaluation of the candidate vaccine in adults older than 50 years of age is planned.Vaccine 08/2013; 31(48). DOI:10.1016/j.vaccine.2013.07.064 · 3.49 Impact Factor