Project description:Human T-leukemia virus 1 (HTLV-1) is an oncogenic retrovirus with no available curative therapy. In-vitro data suggests HTLV-1 may be susceptible to certain HIV-1 antiretroviral compounds but their value, if any, in the context of a clinically-relevant transmission model is unknown. We addressed this knowledge gap by investigating the efficacy of the anti-retroviral compounds, tenofovir and dolutegravir, in preventing HTLV-1 transmission and infection in a humanised mouse model of HTLV-1 subtype c (HTLV-1c) infection, the first of its kind. Characterisation of this model revealed that HTLV-1c and HTLV-1 subtype a (HTLV-1a) showed subtle differences in natural history of disease but not as striking as the differences observed clinically, indicating additional host and environmental contributors to human disease. Single cell RNA sequencing of CD4+ T cell VDJ transcripts revealed poly- and oligoclonal expansion of HTLV-1c-infected CD4+ T cells. We show that tenofovir significantly reduces HTLV-1 transmission in vivo at clinically relevant doses when administered as pre-exposure prophylaxis. Further, tenofovir and dolutegravir combination significantly attenuates viral spread and disease progression during early infection. Our data support the use of tenofovir and dolutegravir against HTLV-1 transmission and early infection. Routine use of these drugs as effective prophylactic agents against HIV-1 infection will facilitate their rapid translation to HTLV-1 clinical trials.
Project description:Nuclear-localized RNA binding proteins are involved in various aspects of RNA metabolism, which in turn modulates gene expression. However, the functions of nuclear-localized RNA binding proteins in plants are poorly understood. Here we report the functions of two proteins containing RNA recognition motifs, At RZ-1B and At RZ-1C, in Arabidopsis. At RZ-1B and At RZ-1C were localized to nuclear speckles and interacted with a spectrum of serine/arginine-rich (SR) proteins through their C-termini. At RZ-1C preferentially bound to purine-rich RNA sequences in vitro through its N-terminal RNA recognition motif. Disrupting the RNA-binding activity of At RZ-1C with SR proteins through over-expression of the C-terminus of At RZ-1C conferred defective phenotypes similar to those observed in At rz-1b/At rz-1c double mutants, including delayed seed germination, reduced stature, and serrated leaves. Loss of function of At RZ-1B and At RZ-1C was accompanied by defective splicing of many genes and global perturbation of gene expression. In addition, we found that At RZ-1C directly targeted FLC, promoting efficient splicing of FLC introns and likely also repressing FLC transcription. Our findings highlight the critical role of At RZ-1B/1C in regulating RNA splicing, gene expression, and many key aspects of plant development via interaction with proteins including SR proteins.
Project description:SREBF-1c is a transcription factor regulating fatty acid biosynthesis. We have charaterized the impact of the abcence of SREBF-1c on the development of peripheral neuropathy In this dataset we included expression data from dissected sciatic nerve from 10 months old SREBF-1c KO mice and relative littermates.
2015-02-10 | GSE65754 | GEO
Project description:Promoter evolution in HIV-1C establishes latent reservoirs highly resistant to reversal
Project description:Nuclear-localized RNA binding proteins are involved in various aspects of RNA metabolism, which in turn modulates gene expression. However, the functions of nuclear-localized RNA binding proteins in plants are poorly understood. Here we report the functions of two proteins containing RNA recognition motifs, At RZ-1B and At RZ-1C, in Arabidopsis. At RZ-1B and At RZ-1C were localized to nuclear speckles and interacted with a spectrum of serine/arginine-rich (SR) proteins through their C-termini. At RZ-1C preferentially bound to purine-rich RNA sequences in vitro through its N-terminal RNA recognition motif. Disrupting the RNA-binding activity of At RZ-1C with SR proteins through over-expression of the C-terminus of At RZ-1C conferred defective phenotypes similar to those observed in At rz-1b/At rz-1c double mutants, including delayed seed germination, reduced stature, and serrated leaves. Loss of function of At RZ-1B and At RZ-1C was accompanied by defective splicing of many genes and global perturbation of gene expression. In addition, we found that At RZ-1C directly targeted FLC, promoting efficient splicing of FLC introns and likely also repressing FLC transcription. Our findings highlight the critical role of At RZ-1B/1C in regulating RNA splicing, gene expression, and many key aspects of plant development via interaction with proteins including SR proteins. mRNA-seq to look at the transcriptome and splicing differences between wild type and At rz-1b At rz-1c mutant of Arabidopsis thaliana
Project description:We carried out chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to explore the difference of the genome-wide dynamics of histone modifications and HP1 in PfRrp6-DD-1C line.
Project description:Epstein-Barr virus (EBV) causes Burkitt, Hodgkin, and post-transplant B-cell lymphomas. How EBV remodels metabolic pathways to support rapid B-cell outgrowth remains largely unknown. To gain insights, primary human B-cells were profiled by tandem-mass-tag based proteomics at rest and at 9 time points after infection. >8000 host and 29 viral proteins were quantified, revealing mitochondrial remodeling and induction of one-carbon (1C) metabolism. EBV-encoded EBNA2 and its target MYC were required for upregulation of the central mitochondrial 1C enzyme MTHFD2, which played key roles in EBV-driven B-cell growth and survival. MTHFD2 was critical for maintaining elevated NADPH levels in infected cells, and oxidation of mitochondrial NADPH diminished B-cell proliferation. Tracing studies underscored contributions of 1C to nucleotide synthesis, NADPH production and redox defense. EBV upregulated import and synthesis of serine to augment 1C flux. Our results highlight EBV-induced 1C as a potential therapeutic target and provide a new paradigm for viral onco-metabolism.