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O Voinnet

Publications and source records attributed to O Voinnet.

9 recordsLinked to original sources
PubMed2006

Viruses, microRNAs and cancer.

Viruses represent one of the main factors that cause normal cells to proliferate and to become malignant: up to 15% of all human cancers are associated with single or multiple virus infections, and several viruses have been recognized as causal agents of specific types of cancer. Viruses have evolved many strategies to prevent infected cells from becoming apoptotic and to evade the innate and adaptive immune responses of their hosts. The recent discovery that Epstein-Barr virus and other herpesviruses produce their own sets of micro (mi)RNAs brings an additional layer of complexity in this ongoing host-virus arms race and changes our initial views of the antiviral roles of RNA silencing in plants and insects. It seems that, rather than being inhibited by this process, many mammalian viruses can usurp or divert the host RNA silencing machinery to their advantage. Viral-encoded miRNAs can act both in cis, to ensure accurate expression of viral genomes, and in trans, to modify the expression of host transcripts. Here, we review the current knowledge on viral miRNAs and discuss how mammalian viruses can also perturb host miRNA expression. Those recent findings provide new insights into the role of viruses and miRNAs in cancer development.

Animals↗
PubMed2001

RNA silencing as a plant immune system against viruses.

"RNA silencing" refers to related processes of post-trancriptional control of gene expression found in plants, animals and fungi. A unifying feature of RNA silencing is that it mediates sequence-specific degradation of target transcripts, recruiting RNA molecules of 21-23 nucleotides as specificity determinants. In higher plants, RNA silencing serves as an adaptive, antiviral defence system, which is transmitted systemically in response to localized virus challenge. Plant viruses have elaborated a variety of counter-defensive measures to overcome the host silencing response. One of these strategies is to produce proteins that target the cell autonomous or signalling steps of RNA silencing. It is not known whether a similar antiviral mechanism also operates in animal cells.

Animals↗
PubMed2000

A viral movement protein prevents spread of the gene silencing signal in Nicotiana benthamiana.

In plants, viruses induce an RNA-mediated defense that is similar to posttranscriptional gene silencing (PTGS) of transgenes. Here we demonstrate with potato virus X (PVX) that PTGS operates as a systemic, sequence-specific defense system. However, in grafting experiments or with movement defective forms of PVX, we could not detect systemic silencing unless the 25 kDa viral movement protein (p25) was made nonfunctional. Investigation of p25 revealed two branches to the PTGS pathway that converge in the production of 25 nucleotide RNAs corresponding to the target RNA. One of these branches is unique to virus-induced PTGS and is not affected by p25. The second branch is common to both virus- and transgene-induced PTGS, is blocked by p25, and is likely to generate the systemic silencing signal.

Gene Deletion↗
PubMed1999

Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants.

In transgenic and nontransgenic plants, viruses are both initiators and targets of a defense mechanism that is similar to posttranscriptional gene silencing (PTGS). Recently, it was found that potyviruses and cucumoviruses encode pathogenicity determinants that suppress this defense mechanism. Here, we test diverse virus types for the ability to suppress PTGS. Nicotiana benthamiana exhibiting PTGS of a green fluorescent protein transgene were infected with a range of unrelated viruses and various potato virus X vectors producing viral pathogenicity factors. Upon infection, suppression of PTGS was assessed in planta through reactivation of green fluorescence and confirmed by molecular analysis. These experiments led to the identification of three suppressors of PTGS and showed that suppression of PTGS is widely used as a counter-defense strategy by DNA and RNA viruses. However, the spatial pattern and degree of suppression varied extensively between viruses. At one extreme, there are viruses that suppress in all tissues of all infected leaves, whereas others are able to suppress only in the veins of new emerging leaves. This variation existed even between closely related members of the potexvirus group. Collectively, these results suggest that virus-encoded suppressors of gene silencing have distinct modes of action, are targeted against distinct components of the host gene-silencing machinery, and that there is dynamic evolution of the host and viral components associated with the gene-silencing mechanism.

DNA Viruses↗
PubMed1999

RNA-DNA interactions and DNA methylation in post-transcriptional gene silencing.

Post-transcriptional gene silencing (PTGS) is a homology-dependent process that reduces cytoplasmic RNA levels. In several experimental systems, there is also an association of PTGS with methylation of DNA. To investigate this association, we used plants carrying a transgene encoding the green fluorescent protein (GFP). Gene silencing was induced using potato virus X RNA vectors carrying parts of the coding sequence or the promoter of the GFP transgene. In each instance, homology-based, RNA-directed methylation was associated with silencing. When the GFP-transcribed region was targeted, PTGS affected both transgene and viral RNA levels. When methylation was targeted to a promoter region, transgene RNA levels were reduced; however, viral RNA levels were unaffected. For comparison, we induced PTGS of the gene encoding the endogenous ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) small subunit (rbcS) by inoculation with potato virus X-rbcS. In this example, no methylation of the rbcS DNA was associated with the reduction in rbcS transcript levels, and viral RNA levels were unaffected. Finally, we investigated DNA methylation by using GFP-transformed plants in which PTGS was induced by localized introduction of a T-DNA carrying GFP sequences. In these plants, there was methylation of a GFP transgene associated with systemic spread of a gene-silencing signal from the infiltrated part of the plant. This transgene methylation was not affected when systemic PTGS was blocked by suppressors of silencing encoded by potato virus Y and cucumber mosaic virus. Combined, these data support an epigenetic model of PTGS in which transgene methylation is associated with an RNA-DNA interaction that ensures that PTGS is maintained.

DNA Methylation↗
PubMed1998

Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana benthamiana.

Post-transcriptional gene silencing (PTGS) of a green fluorescent protein (GFP) transgene is suppressed in Nicotiana benthamiana plants infected with potato virus Y (PVY) or with cucumber mosaic virus (CMV), but not in plants infected with potato virus X (PVX). By expressing PVY and CMV-encoded proteins in a PVX vector we have shown that the viral suppressors of gene silencing are the HCPro of PVY and the 2b protein of CMV. The HCPro acts by blocking the maintenance of PTGS in tissues where silencing had already been set, whereas the 2b protein prevents initiation of gene silencing at the growing points of the plants. Combined with previous findings that viruses are both activators and targets of PTGS, these data provide compelling evidence that PTGS represents a natural mechanism for plant protection against viruses.

Cucumovirus↗
PubMed1998

Systemic spread of sequence-specific transgene RNA degradation in plants is initiated by localized introduction of ectopic promoterless DNA.

Systemic, posttranscriptional silencing of transgenes in Nicotiana benthamiana was initiated in localized regions of the plant by introduction of transgene-homologous DNA fragments, including those without a promoter. Following this initiation step, a sequence-specific signal of gene silencing spread from cells that had received the ectopic DNA via a relay mechanism that employs plasmodesmatal and phloem channels. The nature of this mechanism, the mode of its initiation, and the ability of the signal to move long distances indicate the existence of a sequence-specific signaling mechanism in plants that may have roles in developmental control as well as in protection against transposons and viruses.

Genes, Plant↗
PubMed1998

Initiation and maintenance of virus-induced gene silencing

The phytoene desaturase (PDS) gene of Nicotiana benthamiana was silenced in plants infected with potato virus X (PVX) vectors carrying PDS inserts, and a green fluorescent protein (GFP) transgene was silenced in plants infected with PVX-GFP. This virus-induced gene silencing (VIGS) is post-transcriptional and cytoplasmic because it is targeted against exons rather than introns of PDS RNA and against viral RNAs. Although PDS and GFP RNAs are most likely targeted through the same mechanism, the VIGS phenotypes differed in two respects. PDS mRNA was targeted by VIGS in all green tissue of the PVX-PDS-infected plant, whereas PVX-PDS was not affected. In contrast, VIGS of the GFP was targeted against PVX-GFP. Initially, VIGS of the GFP was initiated in all green tissues, as occurred with PDS VIGS. However, after 30 days of infection, the GFP VIGS was no longer initiated in newly emerging leaves, although it was maintained in tissue in which it had already been initiated. Based on these analyses, we propose a model for VIGS in which the initiation of VIGS is dependent on the virus and maintenance of it is virus independent.

Journal Article↗