As virus diseases cannot be controlled by traditional plant protection methods, the risk of their spread have to be minimized on vegetatively propagated plants, such as grapevine. Metagenomic approaches used for virus diagnostics offer a unique opportunity to reveal the presence of all viral pathogens in the investigated plant, which is why their application can reduce the risk of using infected material for a new plantation. Here we used a special branch, deep sequencing of virus-derived small RNAs, of this high-throughput method for virus diagnostics, and determined viromes of vineyards in Hungary. With NGS of virus-derived small RNAs we could detect not only the viruses tested routinely, but also new ones, which had never been described in Hungary before. Virus presence did not correlate with the age of the plantation, moreover phylogenetic analysis of the identified virus isolates suggests that infections are mostly caused by the use of infected propagating material. Our results, validated by other molecular methods, raised further questions to be answered before this method can be introduced as a routine, reliable test for grapevine virus diagnostics.
TGF-β regulates VEGF release by glioma cells in an ALK-5-dependent manner involving SMAD2, SMAD3, and SMAD1/5/8 signaling. This crosstalk between the TGF-β and VEGF pathways may open up new avenues of biomarker-driven exploratory clinical trials focusing on the microenvironment in glioblastoma.
Malignant gliomas are intrinsic brain tumors with a dismal prognosis. They are well-adapted to hypoxic conditions and poorly immunogenic. NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DL).Here we evaluated the impact of miRNA on the expression of NKG2DL in glioma cells including stem-like glioma cells. Three of the candidate miRNA predicted to target NKG2DL were expressed in various glioma cell lines as well as in glioblastomas in vivo: miR-20a, miR-93 and miR-106b. LNA inhibitor-mediated miRNA silencing up-regulated cell surface NKG2DL expression, which translated into increased susceptibility to NK cell-mediated lysis. This effect was reversed by neutralizing NKG2D antibodies, confirming that enhanced lysis upon miRNA silencing was mediated through the NKG2D system. Hypoxia, a hallmark of glioblastomas in vivo, down-regulated the expression of NKG2DL on glioma cells, associated with reduced susceptibility to NK cell-mediated lysis. This process, however, was not mediated through any of the examined miRNA. Accordingly, both hypoxia and the expression of miRNA targeting NKG2DL may contribute to the immune evasion of glioma cells at the level of the NKG2D recognition pathway. Targeting miRNA may therefore represent a novel approach to increase the immunogenicity of glioblastoma.
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