Project description:Individual variations in immune status and function determine responses to infection and contribute to disease severity and outcome. Patients exhibit considerable variation in clinical responses to infection with West Nile virus. We have undertaken a comprehensive characterization of the immune responses of a stratified cohort of patients with a history of West Nile virus infection to identify key mechanisms of resistance and susceptibility. We provide molecular profiles of cellular mechanisms of primary human immune cells defined through multifaceted interrogation including multiplexed gene expression analysis integrated with highly sensitive multidimensional flow cytometry. The availability of reliably curated patient cohorts and data-sharing and data mining techniques of high-throughout investigations should accelerate identification of critical elements of immune resistance to important pathogens
Project description:High throughput sequencing was performed using Illumina HiSeq to identify differentially regulated genes in Culex mosquitoes after West Nile virus infection.
Project description:Individual variations in immune status and function determine responses to infection and contribute to disease severity and outcome. Patients exhibit considerable variation in clinical responses to infection with West Nile virus. We have undertaken a comprehensive characterization of the immune responses of a stratified cohort of patients with a history of West Nile virus infection to identify key mechanisms of resistance and susceptibility. We provide molecular profiles of cellular mechanisms of primary human immune cells defined through multifaceted interrogation including multiplexed gene expression analysis integrated with highly sensitive multidimensional flow cytometry. The availability of reliably curated patient cohorts and data-sharing and data mining techniques of high-throughout investigations should accelerate identification of critical elements of immune resistance to important pathogens Differential gene expression by human PBMCs and macrophages from asymptomatic and severe patients with WNV infection or Poly I:C were generated by microarray.
Project description:We report the full polyprotein genomic sequence of a West Nile virus strain isolated from Eurasian magpies dying with neurologic signs in Greece. Our findings demonstrate the local genetic evolution of the West Nile virus strain responsible for a human disease outbreak in the country that began in 2010.
Project description:Host migration and emerging pathogens are strongly associated, especially with regard to zoonotic diseases. West Nile virus (WNV), a mosquitoborne pathogen capable of causing severe, sometimes fatal, neuroinvasive disease in humans, is maintained in highly mobile avian hosts. Using phylogeographic approaches, we investigated the relationship between WNV circulation in the United States and the flight paths of terrestrial birds. We demonstrated southward migration of WNV in the eastern flyway and northward migration in the central flyway, which is consistent with the looped flight paths of many terrestrial birds. We also identified 3 optimal locations for targeted WNV surveillance campaigns in the United States-Illinois, New York, and Texas. These results illustrate the value of multidisciplinary approaches to surveillance of infectious diseases, especially zoonotic diseases.
Project description:Since its introduction to North America in 1999, West Nile virus (WNV) has had devastating impacts on native host populations, but to date these impacts have been difficult to measure. Using a continental-scale dataset comprised of a quarter-million birds captured over nearly two decades and a recently developed model of WNV risk, we estimated the impact of this emergent disease on the survival of avian populations. We find that populations were negatively affected by WNV in 23 of the 49 species studied (47%). We distinguished two groups of species: those for which WNV negatively impacted survival only during initial spread of the disease (n = 11), and those that show no signs of recovery since disease introduction (n = 12). Results provide a novel example of the taxonomic breadth and persistent impacts of this wildlife disease on a continental scale. Phylogenetic analyses further identify groups (New World sparrows, finches, and vireos) disproportionally affected by temporary or persistent WNV effects, suggesting an evolutionary dimension of disease risk. Identifying the factors affecting the persistence of a disease across host species is critical to mitigating its effects, particularly in a world marked by rapid anthropogenic change.
Project description:Here, we characterize the RIX line CC(032x013)F1, which serves as a mouse model of chronic WNV infection. While studies using C57BL/6 mice have shown that WNV RNA can persist in the CNS up to 3 months post infection in a limited fraction of mice (Appler et al., 2010), to date there is a lack of a robust mouse model of chronic West Nile virus infection that can be used to elucidate the immune responses associated with this viral persistence and chronicity of symptoms described in human patients. Here, we characterize this line in comparison with lines showing either no disease symptoms or significant disease, and suggest a mechanism by which WNV infection can become chronic through alterations in immune responses.
Project description:West Nile virus (WNV) is a vector-borne pathogen that was first detected in the United States in 1999. The natural transmission cycle of WNV involves mosquito vectors and avian hosts, which vary in their competency to transmit the virus. American robins are an abundant backyard species in the United States and appear to have an important role in the amplification and dissemination of WNV. In this study we examine the response of American robins to infection with various WNV doses within the range of those administered by some natural mosquito vectors. Thirty American robins were assigned a WNV dosage treatment and needle inoculated with 10(0.95) PFU, 10(1.26) PFU, 10(2.15) PFU, or 10(3.15) PFU. Serum samples were tested for the presence of infectious WNV and/or antibodies, while oral swabs were tested for the presence of WNV RNA. Five of the 30 (17%) robins had neutralizing antibodies to WNV prior to the experiment and none developed viremia or shed WNV RNA. The proportion of WNV-seronegative birds that became viremic after WNV inoculation increased in a dose dependent manner. At the lowest dose, only 40% (2/5) of the inoculated birds developed productive infections while at the highest dose, 100% (7/7) of the birds became viremic. Oral shedding of WNV RNA followed a similar trend where robins inoculated with the lower two doses were less likely to shed viral RNA (25%) than robins inoculated with one of the higher doses (92%). Viremia titers and morbidity did not increase in a dose dependent manner; only two birds succumbed to infection and, interestingly, both were inoculated with the lowest dose of WNV. It is clear that the disease ecology of WNV is a complex interplay of hosts, vectors, and viral dose delivered.