Browsing by Subject "WNV"
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Item Assessment of U.S. Agriculture Sector and Human Vulnerability to a Rift Valley Fever Outbreak(2011-08-08) Hughes, Randi CatherineForeign animal disease outbreaks can cause substantial economic losses. Policy makers need information on both the vulnerability of the food supply to disease epidemics and the impacts of alternative protection actions. This research focused on the assessment of the U.S. agricultural sector and human vulnerability to a Rift Valley Fever (RVF) outbreak and the value of a select set of alternative disease control strategies. RVF is a vector-borne, zoonotic disease that affects both livestock and humans; thus both animal and human consequences of an outbreak were examined. This research was conducted in two parts. Livestock impact assessment used an integrated epidemic/economic model to examine the extent of RVF spread in the animal population and its consequences plus the outcome of implementing two different control strategies: emergency vaccination and larvicide vector control. The number of infected, aborted, and dead animals is best controlled by coupling vaccination along with larvicide, but results in the second highest median national welfare loss. Therefore, careful decisions must be made as to what actions should be taken. Total national producer welfare is reduced with each scenario, and is more severe than the total national welfare loss (producer, consumer, and processor together). Consumer welfare is increased with each scenario due to a drop in prices of some commodities, and in some instances, an increase in supply as well. The majority of the national welfare loss can be attributed to the producers' and processors' loss in welfare. The highest damages are seen in the regions of the outbreak such as the South Central (SC). Other regions such as the Corn Belt, Lake States, and South East regions also see high damages due to price changes. The outbreak did not have substantial price effect on dairy products, but did have noticeable price changes for live cattle such as heifer calves, stocked yearling, and dairy calves. Prices for substitutes such as pork, chicken, and turkey experienced a price reduction, which can also be a factor resulting in consumer welfare gains. Human impact assessment utilized an inferential procedure for estimating the human consequences which comprise of a cost of illness calculation to assess the dollar cost of human illnesses and deaths, as well as a Disability Adjusted Life Year calculation to give an estimate of the burden of disease on public health as a whole. With potential costs above $2 billion for human illness, and with this number not accounting for loss or damages to other sectors of the economy, it can be highly probable that investing in a human vaccination campaign can be cost-effective and possibly cost-reducing. This cost along with the economic loss of the agriculture sector suggests substantial potential losses to the U.S. if this hypothetical situation were to become reality. Combining total loss estimates from the cost of illness and ASM models, potential damage of a RVF outbreak could range from 121 million to 2.3 billion US 2010$. The results of this study show the economic damages of an outbreak in the livestock population being much greater relative to the outbreak in the human population (roughly 16 times greater). It should be pointed out that both cost estimates are most likely under estimated. The animal outbreak is not incorporating all susceptible livestock (e.g. hogs and goats), and the human illness is not incorporating other damages to society (e.g. damages due to loss of tourism). By providing estimates on the potential economic outcomes, policy makers can better choose where, when, and how to invest their resources.Item Genetic analysis of equine 2', 5'-oligoadenylate synthetase (OASI) and ribonculclease L (RNASEL) polymorphims and association to severe West Nile Virus disease(2009-05-15) Rios, Jonathan JosephWest Nile virus (WNV), a member of the Flaviviridae family of RNA viruses, was first introduced to the United States in 1999 with rapid transmission across a variety of hosts throughout the continental states. Genetic research to identify genes involved in resistance and susceptibility to WNV began in mice, where it was observed that natural populations were resistant or fatally susceptible. Further investigation led to the identification of the Flavivirus resistance gene as the oligoadenylate synthetase 1b gene in mice. A nonsense mutation was found within the coding region of this gene that associated absolutely with susceptibility to WNV. A two-stage association study was conducted to identify similar genetic associations to West Nile encephalitis in naturally susceptible and resistant populations of horses in the United States. Genomic sequence of a majority of the equine 2?,5?-oligoadenylate synthetase 1 (OAS1) gene was assembled by shotgun-sequencing CHORI BAC 100:I10 (3.95X). A contig map spanning the entire gene was constructed, including 8 kilobases of promoter sequence upstream of the first exon. Coding regions of equine OAS1 and ribonuclease L (RNASEL) genes, as well as the OAS1 promoter, were screened for mutations from a random sample of horses of multiple breeds. Numerous polymorphisms were identified for case-control analyses. Analysis using Fisher?s Exact test identified allelic and genotypic associations. Odds ratios were also determined to measure strength of the associations. Case-control analysis of haplotype frequencies identified significant differences in haplotype frequencies between populations and association to West Nile encephalitis. A conserved interferon-stimulated response element was mapped to within 518 basepairs upstream of the transcription start site of OAS1. Promoter polymorphisms were not found to affect induction by interferon-tau; however, additional analyses are necessary to further characterize the equine OAS1 promoter and the host factors involved in regulating expression. Statistical analyses of the genotype data from the case and control populations identified significant associations between polymorphisms of the OAS1 and RNASEL genes with severe West Nile encephalitis. The similarity between human and horse OAS immunity genes suggests that the horse may provide a genetic model to further investigate mammalian SNP-associated viral susceptibility.Item West Nile virus versus the host cell: Identification of host factors that modulate infection(2008-08-27) Felicia Gilfoy Santa Maria Guerra; Peter W. Mason; Robert Davey; Nigel Bourne; Gregg Milligan; Frank Scholle; Don M. EstesThere are two competing aspects of virus-host interactions: (i) those that enhance virus transmission and (ii) those that reduce or prevent viral replication and transmission. Each of these types of interactions is critical and both must be investigated to fully understand viral pathogenesis. Cells encode a variety of molecules which are critical for recognizing viral infections. One such molecule, the dsRNA sensor PKR, has been shown to be important for IFN-beta induction. Therefore, to determine whether PKR was involved in the recognition of WNV infection, cells lacking PKR were infected with WNV and assayed for IFN production. Interestingly, PKR-null cells demonstrated dramatically lower levels of WNV-induced IFN compared to wild type cells. Additionally, chemical inhibition of PKR activity or post-translational gene silencing of PKR expression severely impaired WNV-induced IFN production, suggesting that PKR is critical for the induction of IFN following WNV infection. Further analysis suggested that PKR may be important for the activation of NF-kappaB, suggesting a possible mechanism of IFN-beta induction. Consistent with cell line data, PKR was shown to be critical for WNV-induced IFN production in primary mouse bone marrow-derived dendritic cells.\r\nThe recognition of WNV is an important aspect of controlling infection; however, it is only one side of the story. Host factors which WNV utilizes to facilitate its infection and replication are also key to understanding viral pathogenesis. The presence or absence of specific factors may control the level of viral replication, host tropisms and, ultimately, viral pathogenesis. To identify host co-factors that are essential for WNV infection and/or replication, small interfering RNAs (siRNAs) were used to systematically knockdown host gene products and levels of WNV infection and/or replication was assayed in the absence of these factors. A siRNA library screen identified ten cellular proteins which are essential for WNV infection and/or replication. Two of these genes encoded subunits of the proteasome. Chemical inhibitors of proteasome activity confirmed that the proteasome is critical for efficient WNV replication.