Browsing by Subject "Zika"
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Item Exploring for Municipality-Level Socioeconomic Variables Related to Zika Virus Incidence in Colombia(MDPI, 2021-02-13) Kellemen, Marie; Ye, Jun; Moreno-Madriñan, Max J.; Global Health, School of Public HealthColombia experienced an outbreak of Zika virus infection during September 2015 until July 2016. This study aimed to identify the socioeconomic factors that at the municipality level correlate with this outbreak and therefore could have influenced its incidence. An analysis of publicly available, municipality-aggregated data related to eight potential explanatory socioeconomic variables was conducted. These variables are school dropout, low energy strata, social security system, savings capacity, tax, resources, investment, and debt. The response variable of interest in this study is the number of reported cases of Zika virus infection per people (projected) per square kilometer. Binomial regression models were performed. Results show that the best predictor variables of Zika virus occurrence, assuming an expected inverse relationship with socioeconomic status, are “school”, “energy”, and “savings”. Contrary to expectations, proxies of socioeconomic status such as “investment”, “tax”, and “resources” were associated with an increase in the occurrence of Zika virus infection, while no association was detected for “social security” and “debt”. Energy stratification, school dropout rate, and the percentage of the municipality’s income that is saved conformed to the hypothesized inverse relationship between socioeconomic standing and Zika occurrence. As such, this study suggests these factors should be considered in Zika risk modeling.Item High-throughput cis-regulatory element discovery in the vector mosquito Aedes aegypti(BioMed Central, 2016-05-10) Behura, Susanta K.; Sarro, Joseph; Li, Ping; Mysore, Keshava; Severson, David W.; Emrich, Scott J.; Duman-Scheel, Molly; Department of Medical & Molecular Genetics, IU School of MedicineBACKGROUND: Despite substantial progress in mosquito genomic and genetic research, few cis-regulatory elements (CREs), DNA sequences that control gene expression, have been identified in mosquitoes or other non-model insects. Formaldehyde-assisted isolation of regulatory elements paired with DNA sequencing, FAIRE-seq, is emerging as a powerful new high-throughput tool for global CRE discovery. FAIRE results in the preferential recovery of open chromatin DNA fragments that are not bound by nucleosomes, an evolutionarily conserved indicator of regulatory activity, which are then sequenced. Despite the power of the approach, FAIRE-seq has not yet been applied to the study of non-model insects. In this investigation, we utilized FAIRE-seq to profile open chromatin and identify likely regulatory elements throughout the genome of the human disease vector mosquito Aedes aegypti. We then assessed genetic variation in the regulatory elements of dengue virus susceptible (Moyo-S) and refractory (Moyo-R) mosquito strains. RESULTS: Analysis of sequence data obtained through next generation sequencing of FAIRE DNA isolated from A. aegypti embryos revealed >121,000 FAIRE peaks (FPs), many of which clustered in the 1 kb 5' upstream flanking regions of genes known to be expressed at this stage. As expected, known transcription factor consensus binding sites were enriched in the FPs, and of these FoxA1, Hunchback, Gfi, Klf4, MYB/ph3 and Sox9 are most predominant. All of the elements tested in vivo were confirmed to drive gene expression in transgenic Drosophila reporter assays. Of the >13,000 single nucleotide polymorphisms (SNPs) recently identified in dengue virus-susceptible and refractory mosquito strains, 3365 were found to map to FPs. CONCLUSION: FAIRE-seq analysis of open chromatin in A. aegypti permitted genome-wide discovery of CREs. The results of this investigation indicate that FAIRE-seq is a powerful tool for identification of regulatory DNA in the genomes of non-model organisms, including human disease vector mosquitoes.Item History of Mosquitoborne Diseases in the United States and Implications for New Pathogens(Emerging Infectious Diseases, 2018-05) Moreno-Madriñán, Max J.; Turell, Michael; Environmental Health Science, School of Public HealthThe introduction and spread of West Nile virus and the recent introduction of chikungunya and Zika viruses into the Americas have raised concern about the potential for various tropical pathogens to become established in North America. A historical analysis of yellow fever and malaria incidences in the United States suggests that it is not merely a temperate climate that keeps these pathogens from becoming established. Instead, socioeconomic changes are the most likely explanation for why these pathogens essentially disappeared from the United States yet remain a problem in tropical areas. In contrast to these anthroponotic pathogens that require humans in their transmission cycle, zoonotic pathogens are only slightly affected by socioeconomic factors, which is why West Nile virus became established in North America. In light of increasing globalization, we need to be concerned about the introduction of pathogens such as Rift Valley fever, Japanese encephalitis, and Venezuelan equine encephalitis viruses.Item How satellites can help control the spread of diseases such as Zika(The Conversation US, Inc., 2016-02-15) Moreno-Madriñán, Max Jacobo; Epidemiology, Richard M. Fairbanks School of Public HealthItem Identification of Aedes aegypti cis-regulatory elements that promote gene expression in olfactory receptor neurons of distantly related dipteran insects(BMC, 2018-07-11) Mysore, Keshava; Li, Ping; Duman-Scheel, Molly; Medical and Molecular Genetics, School of MedicineBACKGROUND: Sophisticated tools for manipulation of gene expression in select neurons, including neurons that regulate sexually dimorphic behaviors, are increasingly available for analysis of genetic model organisms. However, we lack comparable genetic tools for analysis of non-model organisms, including Aedes aegypti, a vector mosquito which displays sexually dimorphic behaviors that contribute to pathogen transmission. Formaldehyde-assisted isolation of regulatory elements followed by sequencing (FAIRE-seq) recently facilitated genome-wide discovery of putative A. aegypti cis-regulatory elements (CREs), many of which could be used to manipulate gene expression in mosquito neurons and other tissues. The goal of this investigation was to identify FAIRE DNA elements that promote gene expression in the olfactory system, a tissue of vector importance. RESULTS: Eight A. aegypti CREs that promote gene expression in antennal olfactory receptor neurons (ORNs) were identified in a Drosophila melanogaster transgenic reporter screen. Four CREs identified in the screen were cloned upstream of GAL4 in a transgenic construct that is compatible with transformation of a variety of insect species. These constructs, which contained FAIRE DNA elements associated with the A. aegypti odorant coreceptor (orco), odorant receptor 1 (Or1), odorant receptor 8 (Or8) and fruitless (fru) genes, were used for transformation of A. aegypti. Six A. aegypti strains, including strains displaying transgene expression in all ORNs, subsets of these neurons, or in a sex-specific fashion, were isolated. The CREs drove transgene expression in A. aegypti that corresponded to endogenous gene expression patterns of the orco, Or1, Or8 and fru genes in the mosquito antenna. CRE activity in A. aegypti was found to be comparable to that observed in D. melanogaster reporter assays. CONCLUSIONS: These results provide further evidence that FAIRE-seq, which can be paired with D. melanogaster reporter screening to test FAIRE DNA element activity in select tissues, is a useful method for identification of mosquito cis-regulatory elements. These findings expand the genetic toolkit available for the study of Aedes neurobiology. Moreover, given that the CREs drive comparable olfactory neural expression in both A. aegypti and D. melanogaster, it is likely that they may function similarly in multiple dipteran insects, including other disease vector mosquito species.Item Preparation and Use of a Yeast shRNA Delivery System for Gene Silencing in Mosquito Larvae(Humana Press, 2019) Mysore, Keshava; Hapairai, Limb K.; Wei, Na; Realey, Jacob S.; Scheel, Nicholas D.; Severson, David W.; Duman-Scheel, Molly; Medical and Molecular Genetics, School of MedicineThe mosquito genome projects facilitated research in new facets of mosquito biology, including functional genetic studies in the dengue and Zika virus vector Aedes aegypti and the primary African malaria vector Anopheles gambiae. RNA interference (RNAi) has facilitated gene silencing experiments in both of these disease vector mosquito species and could one day be applied as a new method of vector control. Here, we describe a procedure for the genetic engineering of Saccharomyces cerevisiae (baker’s yeast) that express short hairpin RNA (shRNA) corresponding to mosquito target genes of interest. Following cultivation, which facilitates inexpensive propagation of shRNA, the yeast is inactivated and prepared in a ready-to-use dry tablet formulation that is fed to mosquito larvae. Ingestion of the yeast tablets results in effective larval target gene silencing. This technically straightforward and affordable technique may be applicable to a wide variety of mosquito species and potentially to other arthropods that feed on yeast.Item U.S. pregnant women's knowledge and attitudes about behavioral strategies and vaccines to prevent Zika acquisition(Elsevier, 2018-01-02) Fraiz, Lauren Dapena; de Roche, Ariel; Mauro, Christine; Catallozzi, Marina; Zimet, Gregory D.; Shapiro, Gilla K.; Rosenthal, Susan L.; Pediatrics, School of MedicineINTRODUCTION: Zika virus infection during pregnancy can cause significant infant morbidity. Little is known about pregnant women's attitudes regarding behavioral strategies and hypothetical vaccination to prevent Zika infections and sequelae. METHODS: Pregnant women across the United States (N = 362) completed an online questionnaire regarding attitudes about Zika, including six behavioral prevention strategies (i.e., abstaining from sex, using condoms, not traveling to an area with Zika, their partner not traveling into an area with Zika, using mosquito repellant, wearing long pants and sleeves) and vaccination. RESULTS: Most women (91%) were married/living with the baby's father, 65% were non-Hispanic White, and 71% had been pregnant. Seventy-four percent were worried about Zika, while 30% thought they were knowledgeable about Zika. The mean knowledge score was 5.0 out of 8 (SD = 2.09), and the mean behavioral strategies score was 4.9 out of 12 (SD = 3.7) with a range of 0 (none would be hard to do) to 12 (all would be hard to do). In a multivariable model, having had a sexually transmitted infection, living/traveling in an area with Zika, and worrying about Zika were significantly related to reporting behavioral strategies as hard to do. Seventy-two percent would be willing to be vaccinated. In the multivariable model, living/traveling in an area with Zika, believing they knew a lot about Zika, worrying about Zika, and considering Zika vaccine development as important were significantly associated with willingness to get vaccinated. CONCLUSIONS: Pregnant women were worried about Zika, yet had gaps in their factual knowledge. Most women reported they would get vaccinated if a vaccine was available. Pregnant women who reported themselves as vulnerable (being worried, having lived in or traveled to a Zika area) were more likely to view behavioral strategies as hard to do and to accept vaccination.Item Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity(MDPI, 2019-11-06) Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.; Biochemistry and Molecular Biology, School of MedicineZika virus (ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r2 = 0.9) and DENV-2 (DENV-2 + ZIKV, r2 = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r2 = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs.