Inserção de DNA de Trypanosoma cruzi no genoma de célula hospedeira de mamífero por meio de infecção

Teixeira, Antônio R. L.; Lacava, Z.G.M.; Santana, Jaime M.; Luna, Helena

doi:10.1590/s0037-86821991000100010

Cited by 15 publications

(13 citation statements)

References 11 publications

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“…In order to answer this question we hypothesized that the parasite DNA could be retained in the body and that the resulting genomic alterations could explain the rejection of heart tissue by the host immune system. Thus, we postulated lateral transfer of parasite DNA to the host genome [9], [10].…”

Section: Introductionmentioning

confidence: 99%

“…The choice of Chagas disease as a model to study active LDT is further validated by important host-parasite intrinsic features, such as: 1) T. cruzi intracellular forms leave the parasitophorous vacuole of the host cell and remain free to divide in the cytoplasm [48], [49]; 2) during cell division minicircles are cleaved by topoisomerases [50] and could migrate to the host cell nucleus [51], [52]; 3) and, T. cruzi minicircles, with four adenine- and cytosine-rich (AC-rich) CSBs [18], [19], can mediate kDNA insertion into the host genome. All these factors may influence lateral kDNA transfer (LkDT) from T. cruzi to host cells [9], [10], [20], [53]. Our studies were stimulated by the demonstration of existing LkDT events in close proximity as disclosed by PCR using opposing kDNA primers where minicircle fragments had integrated into the host LINE-1 elements [20].…”

Section: Introductionmentioning

confidence: 99%

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Inheritance of DNA Transferred from American Trypanosomes to Human Hosts

et al. 2010

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Interspecies DNA transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. Lateral DNA transfer events and their inheritance has been challenging to document. In this study we modified a thermal asymmetric interlaced PCR by using additional targeted primers, along with Southern blots, fluorescence techniques, and bioinformatics, to identify lateral DNA transfer events from parasite to host. Instances of naturally occurring human infections by Trypanosoma cruzi are documented, where mitochondrial minicircles integrated mainly into retrotransposable LINE-1 of various chromosomes. The founders of five families show minicircle integrations that were transferred vertically to their progeny. Microhomology end-joining of 6 to 22 AC-rich nucleotide repeats in the minicircles and host DNA mediates foreign DNA integration. Heterogeneous minicircle sequences were distributed randomly among families, with diversity increasing due to subsequent rearrangement of inserted fragments. Mosaic recombination and hitchhiking on retrotransposition events to different loci were more prevalent in germ line as compared to somatic cells. Potential new genes, pseudogenes, and knockouts were identified. A pathway of minicircle integration and maintenance in the host genome is suggested. Thus, infection by T. cruzi has the unexpected consequence of increasing human genetic diversity, and Chagas disease may be a fortuitous share of negative selection. This demonstration of contemporary transfer of eukaryotic DNA to the human genome and its subsequent inheritance by descendants introduces a significant change in the scientific concept of evolutionary biology and medicine.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inheritance of DNA Transferred from American Trypanosomes to Human Hosts

et al. 2010

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“…This understanding has allowed us to hypothesize that the intracellular dividing amastigote form of the parasite may integrate its DNA in the genome of the host cell (Teixeira et al 1991(Teixeira et al , 1994. Such an integration of exogenous DNA into the genome of the host cell may, as a consequence, produce modification of gene expression.…”

mentioning

confidence: 99%

Integration of Trypanosoma cruzi kDNA minicircle sequence in the host genome may be associated with autoimmune serum factors in Chagas disease patients

Simões-Barbosa

Barros

Nitz

et al. 1999

Mem. Inst. Oswaldo Cruz

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“…Early treatment with benzidazole or nifurtimox can eradicate the parasite in 60–90% of patients [189], but some patients still suffer an autoimmune response that affects the heart after the parasite has been eliminated [190,191]. Teixeira et al reported that this immune response is triggered by a HGT event between T. cruzi and human cells which induces the expression of cell surface antigens [192–194]. In addition, T.cruzi may also infect germ line cells and vertically transfer its genetic material to the offspring of the original patient [193,195].…”

Section: Accidental Hgt: Tcruzimentioning

confidence: 99%

Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

Elmer

Christensen

Rege

2013

Journal of Controlled Release

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Horizontal gene transfer (HGT) is widespread amongst prokaryotes, but eukaryotes tend to be far less promiscuous with their genetic information. However, several examples of HGT from pathogens into eukaryotic cells have been discovered and mimicked to improve non-viral gene delivery techniques. For example, several viral proteins and DNA sequences have been used to significantly increase cytoplasmic and nuclear gene delivery. Plant genetic engineering is routinely performed with the pathogenic bacterium Agrobacterium tumefaciens and similar pathogens (e.g. Bartonella henselae) may also be able to transform human cells. Intracellular parasites like Trypanosoma cruzi may also provide new insights into overcoming cellular barriers to gene delivery. Finally, intercellular nucleic acid transfer between host cells will also be briefly discussed. This article will review the unique characteristics of several different viruses and microbes and discuss how their traits have been successfully applied to improve non-viral gene delivery techniques. Consequently, pathogenic traits that originally caused diseases may eventually be used to treat many genetic diseases.

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Inserção de DNA de Trypanosoma cruzi no genoma de célula hospedeira de mamífero por meio de infecção

Cited by 15 publications

References 11 publications

Inheritance of DNA Transferred from American Trypanosomes to Human Hosts

Inheritance of DNA Transferred from American Trypanosomes to Human Hosts

Integration of Trypanosoma cruzi kDNA minicircle sequence in the host genome may be associated with autoimmune serum factors in Chagas disease patients

Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

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