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
Genome analysis linking recent European and African influenza (H5N1) viruses
AbstractSalzberg, S. L., Kingsford, C., Cattoli, G., Spiro, D. J., Janies, D. A., Aly, M. M., Brown, I. H., Couacy-Hymann, E., De Mia, G. M., Do, H. D., Guercio, A., Joannis, T., Ali, A. S. M., Osmani, A., Padalino, I., Saad, M. D., Savić, V., Sengamalay, N. A., Yingst, S., … Capua, I. (n.d.).Publication year
2007Journal title
Emerging Infectious DiseasesVolume
13Issue
5Page(s)
713-718AbstractTo better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted.Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania
AbstractBringaud, F., Müller, M., Cerqueira, G. C., Smith, M., Rochette, A., El-Sayed, N. M. A., Papadopoulou, B., & Ghedin, E. (n.d.).Publication year
2007Journal title
PLoS PathogensVolume
3Issue
9Page(s)
1291-1307AbstractTrypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis), Trypanosoma brucei (sleeping sickness), and Trypanosoma cruzi (Chagas disease). Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements - LmSIDER1 (785 copies) and LmSIDER2 (1,073 copies) - that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are ∼70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3′-untranslated regions (3′UTRs) of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3′UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function.Mining predicted essential genes of Brugia malayi for nematode drug targets
AbstractKumar, S., Chaudhary, K., Foster, J. M., Novelli, J. F., Zhang, Y., Wang, S., Spiro, D., Ghedin, E., & Carlow, C. K. S. (n.d.).Publication year
2007Journal title
PloS oneVolume
2Issue
11AbstractWe report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets, However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. Malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.Quasispecies of bovine enteric and respiratory coronaviruses based on complete genome sequences and genetic changes after tissue culture adaptation
AbstractZhang, X., Hasoksuz, M., Spiro, D., Halpin, R., Wang, S., Vlasova, A., Janies, D., Jones, L. R., Ghedin, E., & Saif, L. J. (n.d.).Publication year
2007Journal title
VirologyVolume
363Issue
1Page(s)
1-10AbstractThe genetic diversity of 2 pairs (AH65 and AH187) of wild type bovine coronaviruses (BCoV) sequenced directly from nasal (respiratory) and rectal (enteric) swabs of two feedlot calves with respiratory and enteric symptoms [Hasoksuz, M., Sreevatsan, S., Cho, K.O., Hoet, A.E., Saif, L.J., 2002b. Molecular analysis of the S1 subunit of the spike glycoprotein of respiratory and enteric bovine coronavirus isolates. Virus Res. 84 (1-2), 101-109.]. was analyzed. Sequence analysis of the complete genomes revealed differences at 123 and 149 nucleotides (nt) throughout the entire genome between the respiratory and enteric strains for samples AH65 and AH187, respectively, indicating the presence of intra-host BCoV quasispecies. In addition, significant numbers of sequence ambiguities were found in the genomes of some BCoV-R and BCoV-E strains, suggesting intra-isolate quasispecies. The tissue culture (TC) passaged counterparts of AH65 respiratory BCoV (AH65-R-TC) and enteric BCoV (AH65-E-TC) were also sequenced after 14 and 15 passages and 1 plaque purification in human rectal tumor cells (HRT-18), respectively. Compared to the parental wild type strains, tissue culture passage generated 104 nt changes in the AH65-E-TC isolate but only 8 nt changes in the AH65-R-TC isolate. Particularly noteworthy, the majority of nucleotide changes in the AH65-E-TC isolate occurred at the identical positions as the mutations occurring in the AH65-R strain from the same animal. These data suggest that BCoV evolves through quasispecies development, and that enteric BCoV isolates are more prone to genetic changes and may mutate to resemble respiratory BCoV strains after tissue culture passage.Sequences necessary for trans-splicing in transiently transfected Brugia malayi
AbstractLiu, C., De Oliveira, A., Higazi, T. B., Ghedin, E., DePasse, J., & Unnasch, T. R. (n.d.).Publication year
2007Journal title
Molecular and Biochemical ParasitologyVolume
156Issue
1Page(s)
62-73AbstractMany genes in parasitic nematodes are both cis- and trans-spliced. Previous studies have demonstrated that a 7 nt element encoded in the first intron of the Brugia malayi 70 kDa heat shock protein (BmHSP70) gene was necessary to permit trans-splicing of transgenic mRNAs in embryos transfected with constructs encoding portions of the BmHSP70 gene. Here we demonstrate that this element (the B. malayi HSP70 trans-splicing motif, or BmHSP70 TSM) is necessary and sufficient to direct trans-splicing of transgenic mRNAs derived from two genes naturally containing this motif. Mutations introduced into any position of the BmHSP70 TSM abrogated its ability to direct trans-splicing. Transgenic mRNAs derived from embryos transfected with constructs containing promoters and associated downstream domains from two normally trans-spliced genes that lack a BmHSP70 TSM homologue (the B. malayi 12 kDa small subunit ribosomal protein (BmRPS12) gene and the B. malayi RNA-binding protein (BmRBP1) gene), were not trans-spliced. Transfer of the BmHSP70 TSM into the first intron of the BmRPS12 gene rendered it competent for trans-splicing. Insertion of the BmHSP70 TSM into the single intron of the BmRBP1 gene did not render it trans-splicing competent. However, tagged constructs of the full-length BmRBP1 gene were trans-splicing competent. An analysis of the first exons and introns of over 200 trans-spliced B. malayi genes found homologues for the BmHSP70 TSM in roughly 25%. Thus, while the BmHSP70 TSM is necessary and sufficient to direct trans-splicing in some genomic contexts, independent trans-splicing signals are employed by other genes.Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes
AbstractDunning Hotopp, J. C., Clark, M. E., Oliveira, D. C. S. G., Foster, J. M., Fischer, P., Muñoz Torres, M. C., Giebel, J. D., Kumar, N., Ishmael, N., Wang, S., Ingram, J., Nene, R. V., Shepard, J., Tomkins, J., Richards, S., Spiro, D. J., Ghedin, E., Slatko, B. E., Tettelin, H., & Werren, J. H. (n.d.).Publication year
2007Journal title
ScienceVolume
317Issue
5845Page(s)
1753-1756AbstractAlthough common among bacteria, lateral gene transfer - the movement of genes between distantly related organisms - is thought to occur only rarely between bacteria and multicellular eukaryotes. However, the presence of endosymbionts, such as Wolbachia pipientis, within some eukaryotic germlines may facilitate bacterial gene transfers to eukaryotic host genomes. We therefore examined host genomes for evidence of gene transfer events from Wolbachia bacteria to their hosts. We found and confirmed transfers into the genomes of four insect and four nematode species that range from nearly the entire Wolbachia genome (<1 megabase) to short (>500 base pairs) insertions. Potential Wolbachia-to-host transfers were also detected computationally in three additional sequenced insect genomes. We also show that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts. Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions.Detection of HHV-6B in post-mortem central nervous system tissue of a post-bone marrow transplant recipient: a multi-virus array analysis.
AbstractYao, K., Akyani, N., Donati, D., Sengamalay, N., Fotheringham, J., Ghedin, E., Bishop, M., Barrett, J., Kashanchi, F., & Jacobson, S. (n.d.).Publication year
2006Journal title
Journal of clinical virology : the official publication of the Pan American Society for Clinical VirologyVolume
37Page(s)
S57-62AbstractBACKGROUND: HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT). OBJECTIVE: To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach. RESULTS: Detection of HHV-6 viral DNA sequence and RNA expression were demonstrated in fresh frozen post-mortem autopsy material derived from the insular cortex using a multi-virus array platform. In addition, PCR analysis by real-time quantitative TaqMan demonstrated high viral burden in multiple brain regions tested. Sequencing analysis of PCR product confirmed the virus to be HHV-6 variant B. CONCLUSIONS: Active infection as demonstrated by expression of viral RNA and high viral load in the CNS suggest a possible pathogenic role of HHV-6 in development neurologic complications post-BMT.Differential HHV-6A gene expression in T Cells and primary human astrocytes based on multi-virus array analysis
AbstractYao, K., Mandel, M., Akyani, N., Maynard, K., Sengamalay, N., Fotheringham, J., Ghedin, E., Kashanchi, F., & Jacobson, S. (n.d.).Publication year
2006Journal title
GLIAVolume
53Issue
8Page(s)
789-798AbstractHuman herpesvirus 6 (HHV-6) is a ubiquitous virus that has been associated with a wide spectrum of diseases, such as exanthem infantum, multiple sclerosis, seizures, encephalitis/meningitis, and more recently, mesial temporal lobe sclerosis. Although HHV-6 is known to predominately infect CD4+ T lymphocytes, its ability to infect neural glial cells has been demonstrated both in vitro and in vivo. Reactivation of latent HHV-6 infection in the brain has recently been suggested to play a role in the development of neuropathogenesis. To investigate the association of viral gene expression and disease pathogenesis, we developed a multi-virus array containing all open reading frames of the HHV-6 virus and other pathogenically related viruses (EBV, HBV, HHV-8, HIV-1, HTLV-1, HTLV-2) to study expression of viral gene transcripts. In this study, we infected CD4+ T lymphocytes and primary human astrocytes derived from brain biopsy material in vitro with the more neurotropic HHV-6A strain. Hierarchal cluster analysis based on gene expression over time suggested a temporally regulated herpesvirus transcription process. Furthermore, we compared viral gene expression in CD4+ T lymphocytes and primary human astrocytes at peak viral load levels (> 10 8 copies of virus/106 cells) at 5 days post-infection. Differential expression of HHV-6 A genes was observed between CD4+ T lymphocytes and primary human astrocytes. Absence of a number of HHV-6 genes detected at 5 days post-infection in primary human astrocytes suggests an alternative replication strategy used by HHV-6 to evade immune detection and allow establishment of persistent infection in neural glial cells.Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements
AbstractBringaud, F., Ghedin, E., Blandin, G., Bartholomeu, D. C., Caler, E., Levin, M. J., Baltz, T., & El-Sayed, N. M. (n.d.).Publication year
2006Journal title
Molecular and Biochemical ParasitologyVolume
145Issue
2Page(s)
158-170AbstractThe ingi and L1Tc non-LTR retrotransposons - which constitute the ingi clade - are abundant in the genome of the trypanosomatid species Trypanosoma brucei and Trypanosoma cruzi, respectively. The corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, Leishmania major. To study the evolution of non-LTR retrotransposons in trypanosomatids, we have analyzed all ingi/L1Tc elements and highly degenerate ingi/L1Tc-related sequences identified in the recently completed T. brucei, T. cruzi and L. major genomes. The coding sequences of 242 degenerate ingi/L1Tc-related elements (DIREs) in all three genomes were reconstituted by removing the numerous frame shifts. Three independent phylogenetic analyses conducted on the conserved domains encoded by these elements show that all DIREs, including the 52 L. major DIREs, form a monophyletic group belonging to the ingi clade. This indicates that the trypanosomatid ancestor contained active mobile elements that have been retained in the Trypanosoma species, but were lost from L. major genome, where only remnants (DIRE) are detectable. All 242 DIREs analyzed group together according to their species origin with the exception of 11 T. cruzi DIREs which are close to the T. brucei ingi/DIRE families. Considering the absence of known horizontal transfer between the African T. brucei and the South-American T. cruzi, this suggests that this group of elements evolved at a lower rate when compared to the other trypanosomatid elements. Interestingly, the only nucleotide sequence conserved between ingi and L1Tc (the first 79 residues) is also present at the 5′-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs.Shared data are key to beating threat from flu [1]
Salzberg, S., Ghedin, E., & Spiro, D. (n.d.). In Nature (1–).Publication year
2006Volume
440Issue
7084Stochastic processes are key determinants of short-term evolution in influenza a virus.
AbstractNelson, M. I., Simonsen, L., Viboud, C., Miller, M. A., Taylor, J., George, K. S., Griesemer, S. B., Ghedin, E., Sengamalay, N. A., Spiro, D. J., Volkov, I., Grenfell, B. T., Lipman, D. J., Taubenberger, J. K., & Holmes, E. C. (n.d.).Publication year
2006Journal title
PLoS PathogensVolume
2Issue
12AbstractUnderstanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis.The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion
AbstractBringaud, F., Bartholomeu, D. C., Blandin, G., Delcher, A., Baltz, T., El-Sayed, N. M. A., & Ghedin, E. (n.d.).Publication year
2006Journal title
Molecular Biology and EvolutionVolume
23Issue
2Page(s)
411-420AbstractThe trypanosomatid protozoan Trypanosoma cruzi contains long autonomous (L1Tc) and short nonautonomous (NARTc) non-long terminal repeat retrotransposons. NARTc (0.25 kb) probably derived from L1Tc (4.9 kb) by 3′-deletion. It has been proposed that their apparent random distribution in the genome is related to the L1Tc-encoded apurinic/apyrimidinic endonuclease (APE) activity, which repairs modified residues. To address this question we used the T. cruzi (CL-Brener strain) genome data to analyze the distribution of all the L1Tc/NARTc elements present in contigs larger than 10 kb. This data set, which represents 0.91 X sequence coverage of the haploid nuclear genome (∼55 Mb), contains 419 elements, including 112 full-length L1Tc elements (14 of which are potentially functional) and 84 full-length NARTc. Approximately half of the full-length elements are flanked by a target site duplication, most of them (87%) are 12 bp long. Statistical analyses of sequences flanking the full-length elements show the same highly conserved pattern upstream of both the L1Tc and NARTc retrotransposons. The two most conserved residues are a guanine and an adenine, which flank the site where first-strand cleavage is performed by the element-encoded endonuclease activity. This analysis clearly indicates that the L1Tc and NARTc elements display relative site specificity for insertion, which suggests that the APE activity is not responsible for first-strand cleavage of the target site.Comparative genomics of trypanosomatid parasitic protozoa
AbstractEl-Sayed, N. M., Myler, P. J., Blandin, G., Berriman, M., Crabtree, J., Aggarwal, G., Caler, E., Renauld, H., Worthey, E. A., Hertz-Fowler, C., Ghedin, E., Peacock, C., Bartholomeu, D. C., Haas, B. J., Tran, A. N., Wortman, J. R., Alsmark, U. C. M., Angiuoli, S., Anupama, A., … Hall, N. (n.d.).Publication year
2005Journal title
ScienceVolume
309Issue
5733Page(s)
404-409+435AbstractA comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.Genomic and proteomic approaches for Chagas' disease: Critical analysis of diagnostic methods
AbstractHuete-Pérez, J. A., Flores-Obando, R. E., Ghedin, E., & Caffrey, C. R. (n.d.).Publication year
2005Journal title
Expert Review of Molecular DiagnosticsVolume
5Issue
4Page(s)
521-530AbstractTrypanosoma cruzi is the etiologic agent of Chagas' disease, a chronic inflammatory condition that results in heart and digestive complications. The first draft of the parasite genome is now complete and it is expected that, along with the published genomic and proteomic analyses discussed herein, it will lead to the identification of crucial genes and proteins directly associated with disease. This article reviews the current research trends addressing host-parasite interaction, parasite genetic variability and diagnosis. These advances will certainly bring about major developments not only in our understanding of Trypanosoma cruzi biology, but also in the application of new technologies to disease prevention and control.Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution
AbstractGhedin, E., Sengamalay, N. A., Shumway, M., Zaborsky, J., Feldblyum, T., Subbu, V., Spiro, D. J., Sitz, J., Koo, H., Bolotov, P., Dernovoy, D., Tatusova, T., Bao, Y., St George, K., Taylor, J., Lipman, D. J., Fraser, C. M., Taubenberger, J. K., & Salzberg, S. L. (n.d.).Publication year
2005Journal title
NatureVolume
437Issue
7062Page(s)
1162-1166AbstractInfluenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.Mimivirus relatives in the Sargasso sea
AbstractGhedin, E., & Claverie, J. M. (n.d.).Publication year
2005Journal title
Virology JournalVolume
2AbstractThe discovery and genome analysis of Acanthamoeba polyphaga Mimivirus, the largest known DNA virus, challenged much of the accepted dogma regarding viruses. Its particle size (>400 nm), genome length (1.2 million bp) and huge gene repertoire (911 protein coding genes) all contribute to blur the established boundaries between viruses and the smallest parasitic cellular organisms. Phylogenetic analyses also suggested that the Mimivirus lineage could have emerged prior to the individualization of cellular organisms from the three established domains, triggering a debate that can only be resolved by generating and analyzing more data. The next step is then to seek some evidence that Mimivirus is not the only representative of its kind and determine where to look for new Mimiviridae. An exhaustive similarity search of all Mimivirus predicted proteins against all publicly available sequences identified many of their closest homologues among the Sargasso Sea environmental sequences. Subsequent phylogenetic analyses suggested that unknown large viruses evolutionarily closer to Mimivirus than to any presently characterized species exist in abundance in the Sargasso Sea. Their isolation and genome sequencing could prove invaluable in understanding the origin and diversity of large DNA viruses, and shed some light on the role they eventually played in the emergence of eukaryotes.The genome of the African trypanosome Trypanosoma brucei
AbstractBerriman, M., Ghedin, E., Hertz-Fowler, C., Blandin, G., Renauld, H., Bartholomeu, D. C., Lennard, N. J., Caler, E., Hamlin, N. E., Haas, B., Böhme, U., Hannick, L., Aslett, M. A., Shallom, J., Marcello, L., Hou, L., Wickstead, B., Alsmark, U. C. M., Arrowsmith, C., … El-Sayed, N. M. (n.d.).Publication year
2005Journal title
ScienceVolume
309Issue
5733Page(s)
416-422AbstractAfrican trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabasesized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.The genome sequence of Trypanosoma cruzi, etiologic agent of chagas disease
AbstractEl-Sayed, N. M., Myler, P. J., Bartholomeu, D. C., Nilsson, D., Aggarwal, G., Tran, A. N., Ghedin, E., Worthey, E. A., Delcher, A. L., Blandin, G., Westenberger, S. J., Caler, E., Cerqueira, G. C., Branche, C., Haas, B., Anupama, A., Arner, E., Åslund, L., Attipoe, P., … Andersson, B. (n.d.).Publication year
2005Journal title
ScienceVolume
309Issue
5733Page(s)
409-415+435AbstractWhole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.The Wolbachia genome of Brugia malayi: Endosymbiont evolution within a human pathogenic nematode
AbstractFoster, J., Ganatra, M., Kamal, I., Ware, J., Makarova, K., Ivanova, N., Bhattacharyya, A., Kapatral, V., Kumar, S., Posfai, J., Vincze, T., Ingram, J., Moran, L., Lapidus, A., Omelchenko, M., Kyrpides, N., Ghedin, E., Wang, S., Goltsman, E., … Slatko, B. (n.d.).Publication year
2005Journal title
PLoS BiologyVolume
3Issue
4Page(s)
599-614AbstractComplete genome DNA sequence and analysis is presented for Wolbachia, the obligate alpha-proteobacterial endosymbiont required for fertility and survival of the human filarial parasitic nematode Brugia malayi. Although, quantitatively, the genome is even more degraded than those of closely related Rickettsia species, Wolbachia has retained more intact metabolic pathways. The ability to provide riboflavin, flavin adenine dinucleotide, heme, and nucleotides is likely to be Wolbachia's principal contribution to the mutualistic relationship, whereas the host nematode likely supplies amino acids required for Wolbachia growth. Genome comparison of the Wolbachia endosymbiont of B. malayi (wBm) with the Wolbachia endosymbiont of Drosophila melanogaster (wMel) shows that they share similar metabolic trends, although their genomes show a high degree of genome shuffling. In contrast to wMel, wBm contains no prophage and has a reduced level of repeated DNA. Both Wolbachia have lost a considerable number of membrane biogenesis genes that apparently make them unable to synthesize lipid A, the usual component of proteobacterial membranes. However, differences in their peptidoglycan structures may reflect the mutualistic lifestyle of wBm in contrast to the parasitic lifestyle of wMel. The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems. Analysis of this first sequenced endosymbiont genome from a filarial nematode provides insight into endosymbiont evolution and additionally provides new potential targets for elimination of cutaneous and lymphatic human filarial disease.Whole-genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses
AbstractHolmes, E. C., Ghedin, E., Miller, N., Taylor, J., Bao, Y., St. George, K., Grenfell, B. T., Salzberg, S. L., Fraser, C. M., Lipman, D. J., & Taubenberger, J. K. (n.d.).Publication year
2005Journal title
PLoS BiologyVolume
3Issue
9Page(s)
1579-1589AbstractUnderstanding the evolution of influenza A viruses in humans is important for surveillance and vaccine strain selection. We performed a phylogenetic analysis of 156 complete genomes of human H3N2 influenza A viruses collected between 1999 and 2004 from New York State, United States, and observed multiple co-circulating clades with different population frequencies. Strikingly, phylogenies inferred for individual gene segments revealed that multiple reassortment events had occurred among these clades, such that one clade of H3N2 viruses present at least since 2000 had provided the hemagglutinin gene for all those H3N2 viruses sampled after the 2002-2003 influenza season. This reassortment event was the likely progenitor of the antigenically variant influenza strains that caused the A/Fujian/411/2002-like epidemic of the 2003-2004 influenza season. However, despite sharing the same hemagglutinin, these phylogenetically distinct lineages of viruses continue to co-circulate in the same population. These data, derived from the first large-scale analysis of H3N2 viruses, convincingly demonstrate that multiple lineages can co-circulate, persist, and reassort in epidemiologically significant ways, and underscore the importance of genomic analyses for future influenza surveillance.A gene family of cathepsin L-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodeling
AbstractGuiliano, D. B., Hong, X., McKerrow, J. H., Blaxter, M. L., Oksov, Y., Liu, J., Ghedin, E., & Lustigman, S. (n.d.).Publication year
2004Journal title
Molecular and Biochemical ParasitologyVolume
136Issue
2Page(s)
227-242AbstractCysteine proteinases are involved in a variety of important biological processes and have been implicated in molting and tissue remodeling in free living and parasitic nematodes. We show that in the lymphatic filarial nematode Brugia pahangi molting of third-stage larvae (L3) to fourth-stage larvae is dependent on the activity of a cathepsin L-like cysteine protease (CPL), which can be detected in the excretory/secretory (ES) products of molting L3. Directed cloning of a cysteine protease gene in B. pahangi and analysis of the expressed sequence tag (EST) and genomic sequences of the closely related human lymphatic filarial nematode Brugia malayi have identified a family of CPLs. One group of these enzymes, Bm-cpl-1, -4, -5 and Bp-cpl-4, is highly expressed in the B. malayi and B. pahangi infective L3 larvae. Immunolocalization indicates that the corresponding enzymes are synthesized and stored in granules of the glandular esophagus of L3 and released during the molting process. Functional analysis of these genes in Brugia and closely related CPL genes identified in the filarial nematode Onchocerca volvulus and the free living model nematode Caenorhabditis elegans indicate that these genes are also involved in cuticle and eggshell remodeling.Gene synteny and evolution of genome architecture in trypanosomatids
AbstractGhedin, E., Bringaud, F., Peterson, J., Myler, P., Berriman, M., Ivens, A., Andersson, B., Bontempi, E., Eisen, J., Angiuoli, S., Wanless, D., Von Arx, A., Murphy, L., Lennard, N., Salzberg, S., Adams, M. D., White, O., Hall, N., Stuart, K., … El-Sayed, N. M. A. (n.d.).Publication year
2004Journal title
Molecular and Biochemical ParasitologyVolume
134Issue
2Page(s)
183-191AbstractThe trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.LdARF1 in trafficking and structural maintenance of the trans-Golgi cisternal network in the protozoan pathogen Leishmania donovani
AbstractPorter-Kelley, J. M., Gerald, N. J., Engel, J. C., Ghedin, E., & Dwyer, D. M. (n.d.).Publication year
2004Journal title
TrafficVolume
5Issue
11Page(s)
868-883AbstractAdenosine diphosphate ribosylation factors (ARFs) are small guanosine-5′-triphosphatases that are essential in vesicular trafficking and in the maintenance of the Golgi network. In this report, we identified a homolog of the mammalian ARF1 in the human pathogenic protozoan parasite, Leishmania donovani (Ld). Ld ARF1 is a 549 bp gene encoding a 183-amino acid deduced protein of ∼20 kDa. We demonstrated by Southern blot analysis that there are at least two copies of ARF1 in the Ld genome. Moreover, Northern blot analysis revealed that Ld ARF1 is expressed on a 1.35 kb transcript in both the insect vector (promastigotes) and mammalian host (amastigotes) forms of this parasite. Fluorescent microscopy studies using Ld promastigotes episomally transfected with an ARFI::GFP (green fluorescent protein) chimeric construct showed that such chimeras appeared to localize to the Golgi region of these organisms. This observation was verified by immunoelectron microscopy using an anti-GFP antibody. Such studies also revealed that Ld ARF1::GFP chimeras localized to trans-Golgi vesicles, the flagellar pocket/reservoir and other vesicles located between the trans-Golgi network and flagellar pocket in these apically polarized cells. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching experiments revealed both the dynamic binding and releasing activity of Ld ARF1 from the Golgi network in these parasites. Further, episomal expression of a constitutively active ("on") ARF1 (Q71L mutation) resulted in the aberrant swelling and distended-structure of the trans-Golgi cisternae in these cells. These results show that Ld ARF1 is transiently associated with the Golgi network and plays a role in the structural maintenance of this organelle in these important human pathogens.Mechanisms of HTLV-1 transformation.
AbstractKehn, K., Berro, R., De La Fuente, C., Strouss, K., Ghedin, E., Dadgar, S., Bottazzi, M. E., Pumfery, A., & Kashanchi, F. (n.d.).Publication year
2004Journal title
Frontiers in bioscience : a journal and virtual libraryVolume
9Page(s)
2347-2372AbstractHTLV-1 is the etiological agent of the fatal disease adult T-cell leukemia. The virus encodes many proteins including several accessory proteins, p12I, p13II, p27I, and p30II, whose roles have recently begun to be elucidated. These accessory proteins are important in T-cell activation, transcriptional regulation, viral persistence, and virus assembly. The viral oncogene Tax is thought to be largely responsible for tumorigenesis, although the precise mechanisms underlying transformation are not completely understood. Tax has a profound impact on transcription, cell growth regulation, genomic stability and apoptosis. This review will provide possible contributions of the accessory proteins to transformation as well as highlight the alterations of the above-mentioned cellular events by Tax. Animal models of both Tax and the accessory proteins are also included based on the essential information on the transformation process in vivo that they provide.Role of viral regulatory and accessory proteins in HIV-1 replication.
AbstractSeelamgari, A., Maddukuri, A., Berro, R., De La Fuente, C., Kehn, K., Deng, L., Dadgar, S., Bottazzi, M. E., Ghedin, E., Pumfery, A., & Kashanchi, F. (n.d.).Publication year
2004Journal title
Frontiers in bioscience : a journal and virtual libraryVolume
9Page(s)
2388-2413AbstractHuman immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immune deficiency syndrome (AIDS), a disease characterized by CD4+ T lymphocyte depletion. HIV-1 replicates actively in a variety of cells by encoding several regulatory (Tat and Rev) and accessory (Vpr, Vif, Vpu, and Nef) proteins. Accessory proteins, thought initially to be dispensable for infection, have now been shown to be important for efficient infection in vivo. Recent evidence suggests that certain viral proteins, like Vif, have evolved to overcome the antiviral mechanisms of the host, while proteins like Nef, which are markers for disease pathogenesis in vivo, help to increase pathogenesis by targeting bystander cells. Thus, these proteins control many aspects of the virus life cycle as well as host cell function, namely gene regulation and apoptosis. Understanding the mechanisms by which the virus is able to successfully replicate in host cells and subsequently cause gradual destruction of the immune system may yield new approaches for therapeutic strategies. In this review, we attempt to integrate information on the role of these regulatory and accessory proteins, emphasizing their interactions with other viral and cellular components, and the subsequent effect on viral replication.