Trypanosoma cruzi elongation factor 1-α: nuclear localization in parasites undergoing apoptosis

Billaut-Mulot, Odile; Fernández-Gómez, Rodolfo; Loyens, Marc; Ouaissi, Ali

doi:10.1016/0378-1119(96)00254-5

Cited by 55 publications

(44 citation statements)

References 21 publications

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“…It is interesting that the cloned, full-length TcG5 gene showed significant homology to the gene encoding elongation factor 1␣ of trypanosomes, noted to be expressed as cytosolic or nuclear protein in different developmental stages (5). The substantial binding of the TcG5-specific antibodies to the surface of epimastigote and amastigote stages in flow cytometry analysis (Fig.…”

Section: Discussionmentioning

confidence: 96%

Utility of the Trypanosoma cruzi Sequence Database for Identification of Potential Vaccine Candidates by In Silico and In Vitro Screening

Bhatia¹,

Sinha²,

Luxon³

et al. 2004

Infect Immun

108

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Glycosylphosphatidylinositol (GPI)-anchored proteins are abundantly expressed in the infective and intracellular stages of Trypanosoma cruzi and are recognized as antigenic targets by both the humoral and cellular arms of the immune system. Previously, we demonstrated the efficacy of genes encoding GPI-anchored proteins in eliciting partially protective immunity to T. cruzi infection and disease, suggesting their utility as vaccine candidates. For the identification of additional vaccine targets, in this study we screened the T. cruzi expressed sequence tag (EST) and genomic sequence survey (GSS) databases. By applying a variety of web-based genomemining tools to the analysis of ϳ2,500 sequences, we identified 348 (37.6%) EST and 260 (17.4%) GSS sequences encoding novel parasite-specific proteins. Of these, 19 sequences exhibited the characteristics of secreted and/or membrane-associated GPI proteins. Eight of the selected sequences were amplified to obtain genes TcG1, TcG2, TcG3, TcG4, TcG5, TcG6, TcG7, and TcG8 (TcG1-TcG8) which are expressed in different developmental stages of the parasite and conserved in the genome of a variety of T. cruzi strains. Flow cytometry confirmed the expression of the antigens encoded by the cloned genes as surface proteins in trypomastigote and/or amastigote stages of T. cruzi. When delivered as a DNA vaccine, genes TcG1-TcG6 elicited a parasitespecific antibody response in mice. Except for TcG5, antisera to genes TcG1-TcG6 exhibited trypanolytic activity against the trypomastigote forms of T. cruzi, a property known to correlate with the immune control of T. cruzi. Taken together, our results validate the applicability of bioinformatics in genome mining, resulting in the identification of T. cruzi membrane-associated proteins that are potential vaccine candidates.

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Section: Discussionmentioning

confidence: 96%

Utility of the Trypanosoma cruzi Sequence Database for Identification of Potential Vaccine Candidates by In Silico and In Vitro Screening

Bhatia¹,

Sinha²,

Luxon³

et al. 2004

Infect Immun

108

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“…cruzi SSU rDNA has approximately 114 copies per genome (Castro et al, 1981), while EF-1α, DHFR-TS and TR are single copy genes (Sullivan and Walsh, 1991;Reche et al, 1994;Billaut-Mulot et al, 1996). The actin gene has three copies per diploid genome (Cevallos et al, 2003), two of them in tandem at one chromosome (copy 1 and copy 2) and the third one in the homolog chromosome (copy 3).…”

Section: Genetic Diversity Of Trypanosoma Cruzimentioning

confidence: 99%

Haplotype distribution of five nuclear genes based on network genealogies and Bayesian inference indicates that Trypanosoma cruzi hybrid strains are polyphyletic

Tomazi¹,

Kawashita²,

Pereira³

et al. 2009

Genet. Mol. Res.

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ABStRAct. Chagas disease is still a major public health problem in Latin America. Its causative agent, Trypanosoma cruzi, can be typed into three major groups, T. cruzi I, T. cruzi II and hybrids. These groups each have specific genetic characteristics and epidemiological distributions. Several highly virulent strains are found in the hybrid group; their origin is still a matter of debate. The null hypothesis is that the hybrids are of polyphyletic origin, evolving independently from various hybridization events. The alternative hypothesis is that all extant hybrid strains originated from a single hybridization event. We sequenced both alleles of genes encoding EF-1α, actin and SSU rDNA of 26 T. cruzi strains and DHFR-TS and TR of 12 strains. This information was used for network genealogy analysis and Bayesian phylogenies. We found T. cruzi I and T. cruzi II to be monophyletic and that all hybrids had different combinations of T. cruzi I and T. cruzi II haplotypes plus hybrid-specif- Trypanosoma cruzi hybrids are polyphyletic ic haplotypes. Bootstrap values (networks) and posterior probabilities (Bayesian phylogenies) of clades supporting the monophyly of hybrids were far below the 95% confidence interval, indicating that the hybrid group is polyphyletic. We hypothesize that T. cruzi I and T. cruzi II are two different species and that the hybrids are extant representatives of independent events of genome hybridization, which sporadically have sufficient fitness to impact on the epidemiology of Chagas disease.

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“…In Trypanosoma cruzi, nuclear localization of EF-1a has been observed in parasites undergoing apoptosis. 97) EF-1d binds with HIV Tat, which is known to induce apoptosis, and shutoŠ host cell mRNA translation (Fig. 2(B)).…”

Section: (5) Cancer and Elongation Factorsmentioning

confidence: 99%

Moonlighting Functions of Polypeptide Elongation Factor 1: From Actin Bundling to Zinc Finger Protein R1-Associated Nuclear Localization

Ejiri

2002

Bioscience, Biotechnology, and Biochemistry

192

168

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Trypanosoma cruzi elongation factor 1-α: nuclear localization in parasites undergoing apoptosis

Cited by 55 publications

References 21 publications

Utility of the Trypanosoma cruzi Sequence Database for Identification of Potential Vaccine Candidates by In Silico and In Vitro Screening

Utility of the Trypanosoma cruzi Sequence Database for Identification of Potential Vaccine Candidates by In Silico and In Vitro Screening

Haplotype distribution of five nuclear genes based on network genealogies and Bayesian inference indicates that Trypanosoma cruzi hybrid strains are polyphyletic

Moonlighting Functions of Polypeptide Elongation Factor 1: From Actin Bundling to Zinc Finger Protein R1-Associated Nuclear Localization

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