Elodie Ghedin
Elodie Ghedin
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Professor of Epidemiology
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Professional overview
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A molecular parasitologist and virologist, Dr. Elodie Ghedin uses genomics tools to explore host-pathogen interactions in filarial worms (which cause River Blindness and Lymphatic Filariasis) and in viral infections. Her laboratory also explores influenza virus diversity in the infected host and the respiratory tract microbiome to understand transmission dynamics.
Dr. Ghedin’s omics-based predictive modeling project aims to predict severe disease outcome of influenza to develop point of care testing, as some people are more prone to severe versus mild influenza infections. Additionally, her Zika research will be used to develop predictive models for Zika disease severity.
In the Ghedin Lab, Dr. Ghedin offers students an opportunity to study genomic characteristics of human parasites and other pathogens. The research is multidisciplinary and draws upon the tools of genomics, molecular virology, and computational biology. Some projects include the study of influenza virus evolution and emergence, the analysis of the microbiome and mycobiome (fungal microbiota) associated with the pathogenesis of lung obstruction and emphysema in HIV patients, and the characterization of endosymbiotic interactions between filarial worms and Wolbachia. Additionally, Dr. Ghedin also collaborates on the GoViral Project.
As biology and diseases are all interrelated, in her Essentials of Public Health Biology class, Dr. Ghedin teaches the importance of having a foundation in human biology in order to work in any area of public health.
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Education
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BS, Biology, McGill University, Montreal, CanadaMS, Environmental Sciences, University of Quebec, Montreal, CanadaPhD, Molecular Parasitology, McGill University, Montreal, Canada
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Honors and awards
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American Academy of Microbiology Fellow (2017)Kavli Frontiers of Science Fellow (2012)MacArthur Fellow (2011)Chancellor’s Distinguished Research Award (2010)
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Areas of research and study
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BiologyGenomicsInfectious DiseasesViral Infections
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Publications
Publications
Stage-specific proteomic expression patterns of the human filarial parasite Brugia malayi and its endosymbiont Wolbachia
AbstractBennuru, S., Meng, Z., Ribeiro, J. M. C., Semnani, R. T., Ghedin, E., Chan, K., Lucas, D. A., Veenstra, T. D., & Nutman, T. B. (n.d.).Publication year
2011Journal title
Proceedings of the National Academy of Sciences of the United States of AmericaVolume
108Issue
23Page(s)
9649-9654AbstractGlobal proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of Brugia malayi, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as "hypothetical," the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex- and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont Wolbachia as well.Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans
AbstractBahl, J., Nelson, M. I., Chan, K. H., Chen, R., Vijaykrishna, D., Halpin, R. A., Stockwell, T. B., Lin, X., Wentworth, D. E., Ghedin, E., Guan, Y., Peiris, J. S. M., Riley, S., Rambaut, A., Holmes, E. C., & Smith, G. J. D. (n.d.).Publication year
2011Journal title
Proceedings of the National Academy of Sciences of the United States of AmericaVolume
108Issue
48Page(s)
19359-19364AbstractPopulations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.The human lung microbiome
AbstractLosada, L., Ghedin, E., Morris, A., Chu, H. W., & Nierman, W. C. (n.d.). In Metagenomics of the Human Body (1–).Publication year
2011Page(s)
117-143AbstractThe human lower respiratory tract is considered sterile in normal healthy individuals (Flanagan et al., 2007; Speert, 2006) despite the fact that every day we breathe in multiple microorganisms present in the air and aspirate thousands of organisms from the mouth and nasopharynx. This apparent sterility is maintained by numerous interrelated components of the lung physical structures such as the mucociliary elevator and components of the innate and adaptive immune systems (discussed below) (reviewed in (Diamond et al., 2000; Gerritsen, 2000)). However, it is possible that the observed sterility might be a result of the laboratory practices applied to study the flora of the lungs. Historically, researchers faced with a set of diseases characterized by a changing and largely cryptic lung microbiome have lacked tools to study lung ecology as a whole and have concentrated on familiar, cultivatable candidate pathogens.Functional analysis of putative operons in Brugia malayi
AbstractLiu, C., Oliveira, A., Chauhan, C., Ghedin, E., & Unnasch, T. R. (n.d.).Publication year
2010Journal title
International Journal for ParasitologyVolume
40Issue
1Page(s)
63-71AbstractOperons are a common mode of gene organization in Caenorhabditis elegans. Similar gene arrangements suggest that functional operons may exist in Brugia malayi. To definitively test this hypothesis, a bicistronic reporter vector consisting of an upstream firefly luciferase gene and a downstream renilla luciferase gene was constructed. The genome was then surveyed to identify 15 gene pairs that were likely to represent operons. Two of four domains upstream of the 5′ gene from these clusters exhibited promoter activity. When constructs replicating the promoter and intergenic arrangement found in the native putative operon were transfected into embryos, both firefly and renilla activities were detected, while constructs with the promoter alone or intergenic region alone produced no activity from the downstream reporter. These data confirm that functional operons exist in B. malayi. Mutation of three U-rich element homologues present in one of the operons resulted in a decrease in downstream renilla reporter activity, suggesting that these were important in mRNA maturation. Hemi-nested reverse transcriptase-PCR assays demonstrated that while the mRNA encoding the native downstream open reading frame of one operon contained an SL1 spliced leader at its 5′ end, the renilla gene mRNA produced from the corresponding transgenic construct did not.Unseasonal transmission of H3N2 influenza A virus during the swine-origin H1N1 pandemic
AbstractGhedin, E., Wentworth, D. E., Halpin, R. A., Lin, X., Bera, J., DePasse, J., Fitch, A., Griesemer, S., Hine, E., Katzel, D. A., Overton, L., Proudfoot, K., Sitz, J., Szczypinski, B., St George, K., Spiro, D. J., & Holmes, E. C. (n.d.).Publication year
2010Journal title
Journal of virologyVolume
84Issue
11Page(s)
5715-5718AbstractThe initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter months. To explore the nature of virus evolution during this influenza "off-season," we conducted a phylogenetic analysis of H1N1 and H3N2 sequences sampled during April to June 2009 in New York State. Our analysis revealed that multiple lineages of both viruses were introduced and cocirculated during this time, as is typical of influenza virus during the winter. Strikingly, however, we also found strong evidence for the presence of a large transmission chain of H3N2 viruses centered on the south-east of New York State and which continued until at least 1 June 2009. These results suggest that the unseasonal transmission of influenza A viruses may be more widespread than is usually supposed.A multi-reservoir model of influenza evolution
Dreisigmeyer, D. W., Rosenfeld, R., DePasse, J. V., Ghedin, E., Price, I., & Clermont, G. (n.d.).Publication year
2009Journal title
J Crit CareVolume
24Issue
3Page(s)
e33-e34Brugia malayi gene expression in response to the targeting of the Wolbachia endosymbiont by tetracycline treatment
AbstractGhedin, E., Hailemariam, T., DePasse, J. V., Zhang, X., Oksov, Y., Unnasch, T. R., & Lustigman, S. (n.d.). In PLoS Neglected Tropical Diseases (10th eds., 1–).Publication year
2009Volume
3AbstractBackground: Brugia malayi, like most human filarial parasite species, harbors an endosymbiotic bacterium of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female. Previous biochemical and genetic studies have established that communication with its endobacterium is essential for survival of the worm. Methodology/Principal findings: We used electron microscopy to examine the effects of antibiotic treatment on Wolbachia cell structure. We have also used microarray and quantitative RT-PCR analyses to examine the regulation of the B. malayi transcripts altered in response to the anti-Wolbachia treatment. Microscopy of worms taken from animals treated with tetracycline for 14 and 21 days (14 d and 21 d) demonstrated substantial morphologic effects on the Wolbachia endobacterium by 14 d and complete degeneration of the endobacterial structures by 21 d. We observed upregulation of transcripts primarily encoding proteins involved in amino acid synthesis and protein translation, and downregulation of transcripts involved in cuticle biosynthesis after both 7 d and 14 d of treatment. In worms exposed to tetracycline in culture, substantial effects on endobacteria morphology were evident by day 3, and extensive death of the endobacteria was observed by day 5. In a detailed examination of the expression kinetics of selected signaling genes carried out on such cultured worms, a bimodal pattern of regulation was observed. The selected genes were upregulated during the early phase of antibiotic treatment and quickly downregulated in the following days. These same genes were upregulated once more at 6 days post-treatment. Conclusions/ Significance: Upregulation of protein translation and amino acid synthesis may indicate a generalized stress response induced in B. malayi due to a shortage of essential nutrients/factors that are otherwise supplied by Wolbachia. Downregulation of transcripts involved in cuticle biosynthesis perhaps reflects a disruption in the normal embryogenic program. This is confirmed by the expression pattern of transcripts that may be representative of the worms' response to Wolbachia in different tissues; the early peak potentially reflects the effect of bacteria death on the embryogenic program while the second peak may be a manifestation of the adult worm response to the affected bacteria within the hypodermis.GeMInA, Genomic Metadata for Infectious Agents, a geospatial surveillance pathogen database
AbstractSchriml, L. M., Arze, C., Nadendla, S., Ganapathy, A., Felix, V., Mahurkar, A., Phillippy, K., Gussman, A., Angiuoli, S., Ghedin, E., White, O., & Hall, N. (n.d.).Publication year
2009Journal title
Nucleic acids researchVolume
38Page(s)
D754-D764AbstractThe Gemina system (http://gemina.igs.umaryland.edu) identifies, standardizes and integrates the outbreak metadata for the breadth of NIAID category A-C viral and bacterial pathogens, thereby providing an investigative and surveillance tool describing the Who [Host], What [Disease, Symptom], When [Date], Where [Location] and How [Pathogen, Environmental Source, Reservoir, Transmission Method] for each pathogen. The Gemina database will provide a greater understanding of the interactions of viral and bacterial pathogens with their hosts and infectious diseases through in-depth literature text-mining, integrated outbreak metadata, outbreak surveillance tools, extensive ontology development, metadata curation and representative genomic sequence identification and standards development. The Gemina web interface provides metadata selection and retrieval of a pathogen's; Infection Systems (Pathogen, Host, Disease, Transmission Method and Anatomy) and Incidents (Location and Date) along with a hosts Age and Gender. The Gemina system provides an integrated investigative and geospatial surveillance system connecting pathogens, pathogen products and disease anchored on the taxonomic ID of the pathogen and host to identify the breadth of hosts and diseases known for these pathogens, to identify the extent of outbreak locations, and to identify unique genomic regions with the DNA Signature Insignia Detection Tool.Helminth genomics: The implications for human health
AbstractBrindley, P. J., Mitreva, M., Ghedin, E., & Lustigman, S. (n.d.).Publication year
2009Journal title
PLoS neglected tropical diseasesVolume
3Issue
10AbstractMore than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings.Mixed infection and the genesis of influenza virus diversity
AbstractGhedin, E., Fitch, A., Boyne, A., Griesemer, S., DePasse, J., Bera, J., Zhang, X., Halpin, R. A., Smit, M., Jennings, L., St. George, K., Holmes, E. C., & Spiro, D. J. (n.d.).Publication year
2009Journal title
Journal of virologyVolume
83Issue
17Page(s)
8832-8841AbstractThe emergence of viral infections with potentially devastating consequences for human health is highly dependent on their underlying evolutionary dynamics. One likely scenario for an avian influenza virus, such as A/H5N1, to evolve to one capable of human-to-human transmission is through the acquisition of genetic material from the A/H1N1 or A/H3N2 subtypes already circulating in human populations. This would require that viruses of both subtypes coinfect the same cells, generating a mixed infection, and then reassort. Determining the nature and frequency of mixed infection with influenza virus is therefore central to understanding the emergence of pandemic, antigenic, and drug-resistant strains. To better understand the potential for such events, we explored patterns of intrahost genetic diversity in recently circulating strains of human influenza virus. By analyzing multiple viral genome sequences sampled from individual influenza patients we reveal a high level of mixed infection, including diverse lineages of the same influenza virus subtype, drug-resistant and -sensitive strains, those that are likely to differ in antigenicity, and even viruses of different influenza virus types (A and B). These results reveal that individuals can harbor influenza viruses that differ in major phenotypic properties, including those that are antigenically distinct and those that differ in their sensitivity to antiviral agents.The early diversification of influenza A/H1N1pdm
AbstractNelson, M., Spiro, D., Wentworth, D., Fan, J., Beck, E., St. George, K., Ghedin, E., Halpin, R., Bera, J., Hine, E., Proudfoot, K., Stockwell, T., Lin, X., Griesemer, S., Bose, M., Jurgens, L., Kumar, S., Viboud, C., Holmes, E., & Henrickson, K. (n.d.).Publication year
2009Journal title
PLoS CurrentsAbstractBackground Since its initial detection in April 2009, the A/H1N1pdm influenza virus has spread rapidly in humans, with over 5,700 human deaths. However, little is known about the evolutionary dynamics of H1N1pdm and its geographic and temporal diversification. Methods Phylogenetic analysis was conducted upon the concatenated coding regions of whole-genome sequences from 290 H1N1pdm isolates sampled globally between April 1 - July 9, 2009, including relatively large samples from the US states of Wisconsin and New York. Results At least 7 phylogenetically distinct viral clades have disseminated globally and co-circulated in localities that experienced multiple introductions of H1N1pdm. The epidemics in New York and Wisconsin were dominated by two different clades, both phylogenetically distinct from the viruses first identified in California and Mexico, suggesting an important role for founder effects in determining local viral population structures. Conclusions Determining the global diversity of H1N1pdm is central to understanding the evolution and spatial spread of the current pandemic, and to predict its future impact on human populations. Our results indicate that H1N1pdm has already diversified into distinct viral lineages with defined spatial patterns.The genome of Brugia malayi - All worms are not created equal
AbstractScott, A. L., & Ghedin, E. (n.d.).Publication year
2009Journal title
Parasitology InternationalVolume
58Issue
1Page(s)
6-11AbstractFilarial nematode parasites, the causative agents of elephantiasis and river blindness, undermine the livelihoods of over one hundred million people in the developing world. Recently, the Filarial Genome Project reported the draft sequence of the ~ 95 Mb genome of the human filarial parasite Brugia malayi - the first parasitic nematode genome to be sequenced. Comparative genome analysis with the prevailing model nematode Caenorhabditis elegans revealed similarities and differences in genome structure and organization that will prove useful as additional nematode genomes are completed. The Brugia genome provides the first opportunity to comprehensively compare the full gene repertoire of a free-living nematode species and one that has evolved as a human pathogen. The Brugia genome also provides an opportunity to gain insight into genetic basis for mutualism, as Brugia, like a majority of filarial species, harbors an endosybiotic bacterium (Wolbachia). The goal of this review is to provide an overview of the results of genomic analysis and how these observations provide new insights into the biology of filarial species.The genome of the blood fluke Schistosoma mansoni
AbstractBerriman, M., Haas, B. J., Loverde, P. T., Wilson, R. A., Dillon, G. P., Cerqueira, G. C., Mashiyama, S. T., Al-Lazikani, B., Andrade, L. F., Ashton, P. D., Aslett, M. A., Bartholomeu, D. C., Blandin, G., Caffrey, C. R., Coghlan, A., Coulson, R., Day, T. A., Delcher, A., Demarco, R., … El-Sayed, N. M. (n.d.).Publication year
2009Journal title
NatureVolume
460Issue
7253Page(s)
352-358AbstractSchistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus
AbstractBrower-Sinning, R., Carter, D. M., Crevar, C. J., Ghedin, E., Ross, T. M., & Benos, P. V. (n.d.).Publication year
2009Journal title
Genome biologyVolume
10Issue
2AbstractBackground: The influenza A virus genome is composed of eight single-stranded RNA segments of negative polarity. Although the hemagglutinin and neuraminidase genes are known to play a key role in host adaptation, the polymerase genes (which encode the polymerase segments PB2, PB1, PA) and the nucleoprotein gene are also important for the efficient propagation of the virus in the host and for its adaptation to new hosts. Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates. Results: Here we show that the folding free energy of the RNA segments may play an equally important role in the evolution and host adaptation of the influenza virus. Folding free energy may affect the stability of the viral RNA and influence the rate of viral protein translation. We found that there is a clear distinction between the avian and human folding free energy distributions for the polymerase and the nucleoprotein genes, with human viruses having substantially higher folding free energy values. This difference is independent of the amino acid composition and the codon bias. Furthermore, the folding free energy values of the commonly circulating human viruses tend to shift towards higher values over the years, after they entered the human population. Finally, our results indicate that the temperature in which the cells grow affects infection efficiency. Conclusions: Our data suggest for the first time that RNA structure stability may play an important role in the emergence and host shift of influenza A virus. The fact that cell temperature affects virus propagation in mammalian cells could help identify those avian strains that pose a higher threat to humans.Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3
AbstractLi, B. W., Rush, A. C., Mitreva, M., Yin, Y., Spiro, D., Ghedin, E., & Weil, G. J. (n.d.).Publication year
2009Journal title
BMC GenomicsVolume
10AbstractBackground: Filarial nematode parasites cause serious diseases such as elephantiasis and river blindness in humans, and heartworm infections in dogs. Third stage filarial larvae (L3) are a critical stage in the life cycle of filarial parasites, because this is the stage that is transmitted by arthropod vectors to initiate infections in mammals. Improved understanding of molecular mechanisms associated with this transition may provide important leads for development of new therapies and vaccines to prevent filarial infections. This study explores changes in gene expression associated with the transition of Brugia malayi third stage larvae (BmL3) from mosquitoes into mammalian hosts and how these changes are affected by radiation. Radiation effects are especially interesting because irradiated L3 induce partial immunity to filarial infections. The underlying molecular mechanisms responsible for the efficacy of such vaccines are unkown. Results: Expression profiles were obtained using a new filarial microarray with 18, 104 64-mer elements. 771 genes were identified as differentially expressed in two-way comparative analyses of the three L3 types. 353 genes were up-regulated in mosquito L3 (L3i) relative to cultured L3 (L3c). These genes are important for establishment of filarial infections in mammalian hosts. Other genes were up-regulated in L3c relative to L3i (234) or irradiated L3 (L3ir) (22). These culture-induced transcripts include key molecules required for growth and development. 165 genes were up-regulated in L3ir relative to L3c; these genes encode highly immunogenic proteins and proteins involved in radiation repair. L3ir and L3i have similar transcription profiles for genes that encode highly immunogenic proteins, antioxidants and cuticle components. Conclusion: Changes in gene expression that normally occur during culture under conditions that support L3 development and molting are prevented or delayed by radiation. This may explain the enhanced immunogenicity of L3ir. Gene Ontology and KEGG analyses revealed altered pathways between L3 types. Energy and "immune pathways" are up-regulated and may be needed for L3i invasion and survival, while growth and development are priorities for L3c. This study has improved our understanding of molecules involved in parasite invasion and immune evasion, potential targets of protective immunity, and molecules required for parasite growth and development.Bovine-like coronaviruses isolated from four species of captive wild ruminants are homologous to bovine coronaviruses, based on complete genomic sequences
AbstractAlekseev, K. P., Vlasova, A. N., Jung, K., Hasoksuz, M., Zhang, X., Halpin, R., Wang, S., Ghedin, E., Spiro, D., & Saif, L. J. (n.d.).Publication year
2008Journal title
Journal of virologyVolume
82Issue
24Page(s)
12422-12431AbstractWe sequenced and analyzed the full-length genomes of four coronaviruses (CoVs), each from a distinct wild-ruminant species in Ohio: sambar deer (Cervus unicolor), a waterbuck (Kobus ellipsiprymnus), a sable antelope (Hippotragus niger), and a white-tailed deer (Odocoileus virginianus). The fecal samples from the sambar deer, the waterbuck, and the white-tailed deer were collected during winter dysentery outbreaks and sporadic diarrhea cases in 1993 and 1994 (H. Tsunemitsu, Z. R. el-Kanawati, D. R. Smith, H. H. Reed, and L. J. Saif, J. Clin. Microbiol. 33:3264-3269, 1995). A fecal sample from a sable antelope was collected in 2003 from an Ohio wild-animal habitat during the same outbreak when a bovine-like CoV from a giraffe (GiCoV) was isolated (M. Hasoksuz, K. Alekseev, A. Vlasova, X. Zhang, D. Spiro, R. Halpin, S. Wang, E. Ghedin, and L. J. Saif, J. Virol. 81:4981-4990, 2007). For two of the CoVs (sambar deer and waterbuck), complete genomes from both the cell culture-adapted and gnotobiotic-calf- passaged strains were also sequenced and analyzed. Phylogenetically, wild-ruminant CoVs belong to group 2a CoVs, with the closest relatedness to recent bovine CoV (BCoV) strains. High nucleotide identities (99.4 to 99.6%) among the wild-ruminant strains and recent BCoV strains (BCoV-LUN and BCoV-ENT, isolated in 1998) further confirm the close relatedness. Comparative genetic analysis of CoVs of captive wild ruminants with BCoV strains suggests that no specific genomic markers are present that allow discrimination between the bovine strains and bovine-like CoVs from captive wild ruminants; furthermore, no specific genetic markers were identified that defined cell cultured or calf-passaged strains or the host origin of strains. The results of this study confirm prior reports of biologic and antigenic similarities between bovine and wild-ruminant CoVs and suggest that cattle may be reservoirs for CoVs that infect captive wild ruminants or vice versa and that these CoVs may represent host range variants of an ancestral CoV.Molecular epidemiology of A/H3N2 and A/H1N1 influenza virus during a single epidemic season in the United States
AbstractNelson, M. I., Edelman, L., Spiro, D. J., Boyne, A. R., Bera, J., Halpin, R., Ghedin, E., Miller, M. A., Simonsen, L., Viboud, C., & Holmes, E. C. (n.d.).Publication year
2008Journal title
PLoS PathogensVolume
4Issue
8AbstractTo determine the spatial and temporal dynamics of influenza A virus during a single epidemic, we examined whole-genome sequences of 284 A/H1N1 and 69 A/H3N2 viruses collected across the continental United States during the 2006-2007 influenza season, representing the largest study of its kind undertaken to date. A phylogenetic analysis revealed that multiple clades of both A/H1N1 and A/H3N2 entered and co-circulated in the United States during this season, even in localities that are distant from major metropolitan areas, and with no clear pattern of spatial spread. In addition, co-circulating clades of the same subtype exchanged genome segments through reassortment, producing both a minor clade of A/H3N2 viruses that appears to have re-acquired sensitivity to the adamantane class of antiviral drugs, as well as a likely antigenically distinct A/H1N1 clade that became globally dominant following this season. Overall, the co-circulation of multiple viral clades during the 2006-2007 epidemic season revealed patterns of spatial spread that are far more complex than observed previously, and suggests a major role for both migration and reassortment in shaping the epidemiological dynamics of human influenza A virus.Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918
AbstractNelson, M. I., Viboud, C., Simonsen, L., Bennett, R. T., Griesemer, S. B., St. George, K., Taylor, J., Spiro, D. J., Sengamalay, N. A., Ghedin, E., Taubenberger, J. K., & Holmes, E. C. (n.d.).Publication year
2008Journal title
PLoS PathogensVolume
4Issue
2AbstractThe H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized.The evolutionary genetics and emergence of avian influenza viruses in wild birds
AbstractDugan, V. G., Chen, R., Spiro, D. J., Sengamalay, N., Zaborsky, J., Ghedin, E., Nolting, J., Swayne, D. E., Runstadler, J. A., Happ, G. M., Senne, D. A., Wang, R., Slemons, R. D., Holmes, E. C., & Taubenberger, J. K. (n.d.).Publication year
2008Journal title
PLoS PathogensVolume
4Issue
5AbstractWe surveyed the genetic diversity among avian influenza virus (AIV) in wild birds, comprising 167 complete viral genomes from 14 bird species sampled in four locations across the United States. These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection. Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment. From this, we propose that AIV in wild birds forms transient "genome constellations," continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.The symbiotic relationship between filarial parasitic nematodes and their Wolbachia endosymbionts - A resource for a new generation of control measures
AbstractGhedin, E., Daehnel, K., Foster, J., Slatko, B., & Lustigman, S. (n.d.).Publication year
2008Journal title
SymbiosisVolume
46Issue
2Page(s)
77-85AbstractFilarial parasites are responsible for millions of human infections each year, mostly in developing parts of the world. International programs supported largely by the World Health Organization have worked to control the impact of onchocerciasis and lymphatic filariasis using mass administration of single or combination drugs for long periods of time in eligible populations. The success of these programs is now being hampered by the probability of programmatic failure in the event of emerging drug resistance. Additional research is critically needed to develop a new generation of tools for the control and treatment of these infections. These would include drugs that target adult worms and vaccines, with the goal to overcome potential resistance to the currently available drugs and complement present control measures. The majority of human filarial parasites carry intracellular symbiotic bacteria, Wolbachia, that appear to be essential for development and reproduction of the parasite. The recent availability of genomic data for both filaria and Wolbachia provides insight into essential aspects of the symbiotic relationship between the endosymbiont and its nematode host. We present an overview of how this knowledge opens up avenues in the identification of new targets for the control of these parasitic infections.Viral genome sequencing by random priming methods
AbstractDjikeng, A., Halpin, R., Kuzmickas, R., DePasse, J., Feldblyum, J., Sengamalay, N., Afonso, C., Zhang, X., Anderson, N. G., Ghedin, E., & Spiro, D. J. (n.d.).Publication year
2008Journal title
BMC GenomicsVolume
9AbstractBackground: Most emerging health threats are of zoonotic origin. For the overwhelming majority, their causative agents are RNA viruses which include but are not limited to HIV, Influenza, SARS, Ebola, Dengue, and Hantavirus. Of increasing importance therefore is a better understanding of global viral diversity to enable better surveillance and prediction of pandemic threats; this will require rapid and flexible methods for complete viral genome sequencing. Results: We have adapted the SISPA methodology 123 to genome sequencing of RNA and DNA viruses. We have demonstrated the utility of the method on various types and sources of viruses, obtaining near complete genome sequence of viruses ranging in size from 3,000-15,000 kb with a median depth of coverage of 14.33. We used this technique to generate full viral genome sequence in the presence of host contaminants, using viral preparations from cell culture supernatant, allantoic fluid and fecal matter. Conclusion: The method described is of great utility in generating whole genome assemblies for viruses with little or no available sequence information, viruses from greatly divergent families, previously uncharacterized viruses, or to more fully describe mixed viral infections.Biologic, antigenic, and full-length genomic characterization of a bovine-like coronavirus isolated from a giraffe
AbstractHasoksuz, M., Alekseev, K., Vlasova, A., Zhang, X., Spiro, D., Halpin, R., Wang, S., Ghedin, E., & Saif, L. J. (n.d.).Publication year
2007Journal title
Journal of virologyVolume
81Issue
10Page(s)
4981-4990AbstractCoronaviruses (CoVs) possess large RNA genomes and exist as quasispecies, which increases the possibility of adaptive mutations and interspecies transmission. Recently, CoVs were recognized as important pathogens in captive wild ruminants. This is the first report of the isolation and detailed genetic, biologic, and antigenic characterization of a bovine-like CoV from a giraffe (Giraffa camelopardalis) in a wild-animal park in the United States. CoV particles were detected by immune electron microscopy in fecal samples from three giraffes with mild-to-severe diarrhea. From one of the three giraffe samples, a CoV (GiCoV-OH3) was isolated and successfully adapted to serial passage in human rectal tumor 18 cell cultures. Hemagglutination assays, receptor-destroying enzyme activity, hemagglutination inhibition, and fluorescence focus neutralization tests revealed close biological and antigenic relationships between the GiCoV-OH3 isolate and selected respiratory and enteric bovine CoV (BCoV) strains. When orally inoculated into a BCoV-seronegative gnotobiotic calf, GiCoV-OH3 caused severe diarrhea and virus shedding within 2 to 3 days. Sequence comparisons and phylogenetic analyses were performed to assess its genetic relatedness to other CoVs. Molecular characterization confirmed that the new isolate belongs to group 2a of the mammalian CoVs and revealed closer genetic relatedness between GiCoV-OH3 and the enteric BCoVs BCoV-ENT and BCoV-DB2, whereas BCoV-Mebus was more distantly related. Detailed sequence analysis of the GiCoV-OH3 spike gene demonstrated the presence of a deletion in toe variable region of the S1 subunit (from amino acid 543 to amino acid 547), which is a region associated with pathogenicity and tissue tropism for other CoVs. The point mutations identified in the structural proteins (by comparing GiCoV-OH3, BCoV-ENT, BCoV-DB2, and BCoV-Mebus) were most conserved among GiCoV-OH3, BCoV-ENT, and BCoV-DB2, whereas most of the point mutations in the nonstructural proteins were unique to GiCoV-OH3. Our results confirm the existence of a bovine-like CoV transmissible to cattle from wild ruminants, namely, giraffes, but with certain genetic properties different from those of BCoVs.Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus
AbstractZhang, X., Hasoksuz, M., Spiro, D., Halpin, R., Wang, S., Stollar, S., Janies, D., Hadya, N., Tang, Y., Ghedin, E., & Saif, L. (n.d.).Publication year
2007Journal title
VirologyVolume
358Issue
2Page(s)
424-435AbstractTransmissible gastroenteritis virus (TGEV) isolates that have been adapted to passage in cell culture maintain their infectivity in vitro but may lose their pathogenicity in vivo. To better understand the genomic mechanisms for viral attenuation, we sequenced the complete genomes of two virulent TGEV strains and their attenuated counterparts: virulent TGEV Miller M6 and attenuated TGEV Miller M60 and virulent TGEV Purdue and attenuated TGEV Purdue P115, together with the ISU-1 strain of porcine respiratory coronavirus (PRCV-ISU-1), a naturally occurring TGEV deletion mutant with an altered respiratory tropism and reduced virulence. Pairwise comparison at both the nucleotide (nt) and amino acid (aa) levels between virulent and attenuated TGEV strains identified a common change in nt 1753 of the spike gene, resulting in a serine to alanine mutation at aa position 585 of the spike proteins of the attenuated TGEV strains. Alanine was also present in this protein in PRCV-ISU-1. Particularly noteworthy, the serine to alanine mutation resides in the region of the major antigenic site A/B (aa 506-706) that elicits neutralizing antibodies and within the domain mediating the cell surface receptor aminopeptidase N binding (aa 522-744). Comparison of the predicted polypeptide products of ORF3b showed significant deletions in the naturally attenuated PRCV-ISU-1 and TGEV Miller M60; these deletions occurred at a common break point, suggesting a related mechanism of recombination that may affect viral virulence or tropism. Sequence comparisons at both genomic and protein levels indicated that PRCV-ISU-1 had a closer relationship with TGEV Miller strains than Purdue strains. Phylogenetic analyses showed that virulence is an evolutionarily labile trait in TGEV and that TGEV strains as a group share a common ancestor with PRCV.Draft genome of the filarial nematode parasite Brugia malayi
AbstractGhedin, E., Wang, S., Spiro, D., Caler, E., Zhao, Q., Crabtree, J., Allen, J. E., Delcher, A. L., Guiliano, D. B., Miranda-Saavedra, D., Angiuoli, S. V., Creasy, T., Amedeo, P., Haas, B., El-Sayed, N. M., Wortman, J. R., Feldblyum, T., Tallon, L., Schatz, M., … Scott, A. L. (n.d.).Publication year
2007Journal title
ScienceVolume
317Issue
5845Page(s)
1756-1760AbstractParasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.Genes encoding putative biogenic amine receptors in the parasitic nematode Brugia malayi
AbstractSmith, K. A., Komuniecki, R. W., Ghedin, E., Spiro, D., & Gray, J. (n.d.).Publication year
2007Journal title
Invertebrate NeuroscienceVolume
7Issue
4Page(s)
227-244AbstractFilarial nematodes, such as Brugia malayi, cause major health problems worldwide. The lack of a vaccine against B. malayi, combined with ineffective chemotherapy against the adult has prompted the examination of biogenic amine receptors (BARs) as possible targets for drug discovery. We employed bioinformatics to identify genes encoding putative B. malayi BARs. Surprisingly, the B. malayi genome contains half of the genes predicted to encode BARs in the genomes of free-living nematodes such as Caenorhabditis elegans or C. briggsae; however, all of the predicted B. malayi receptors have clear orthologues in C. elegans. The B. malayi genes encode each of the major BAR subclasses, including three serotonin, two dopamine and two tyramine/octopamine receptors and the structure of orthologous BAR genes is conserved. We find that potential G-protein coupling and ligand-specificity of individual BARs may be predicted by phylogenetic comparisons. Our results provide a framework for how G-protein coupled receptors may be targeted for drug development in medically important parasitic nematodes.