Microarray study reveals that HIV-1 induces rapid type-I interferon-dependent p53 mRNA up-regulation in human primary CD4+ T cells

<p>Abstract</p> <p>Background</p> <p>Infection with HIV-1 has been shown to alter expression of a large array of host cell genes. However, previous studies aimed at investigating the putative HIV-1-induced modulation of host gene expression have been mostly performed in established human cell lines. To better approximate natural conditions, we monitored gene expression changes in a cell population highly enriched in human primary CD4⁺T lymphocytes exposed to HIV-1 using commercial oligonucleotide microarrays from Affymetrix.</p> <p>Results</p> <p>We report here that HIV-1 influences expression of genes related to many important biological processes such as DNA repair, cellular cycle, RNA metabolism and apoptosis. Notably, expression of the p53 tumor suppressor and genes involved in p53 homeostasis such as GADD34 were up-regulated by HIV-1 at the mRNA level. This observation is distinct from the previously reported p53 phosphorylation and stabilization at the protein level, which precedes HIV-1-induced apoptosis. We present evidence that the HIV-1-mediated increase in p53 gene expression is associated with virus-mediated induction of type-I interferon (i.e. IFN-α and IFN-β).</p> <p>Conclusion</p> <p>These observations have important implications for our understanding of HIV-1 pathogenesis, particularly in respect to the virus-induced depletion of CD4⁺T cells.</p

Exon level transcriptomic profiling of HIV-1-infected CD4(+) T cells reveals virus-induced genes and host environment favorable for viral replication.

HIV-1 is extremely specialized since, even amongst CD4(+) T lymphocytes (its major natural reservoir in peripheral blood), the virus productively infects only a small proportion of cells under an activated state. As the percentage of HIV-1-infected cells is very low, most studies have so far failed to capture the precise transcriptomic profile at the whole-genome scale of cells highly susceptible to virus infection. Using Affymetrix Exon array technology and a reporter virus allowing the magnetic isolation of HIV-1-infected cells, we describe the host cell factors most favorable for virus establishment and replication along with an overview of virus-induced changes in host gene expression occurring exclusively in target cells productively infected with HIV-1. We also establish that within a population of activated CD4(+) T cells, HIV-1 has no detectable effect on the transcriptome of uninfected bystander cells at early time points following infection. The data gathered in this study provides unique insights into the biology of HIV-1-infected CD4(+) T cells and identifies genes thought to play a determinant role in the interplay between the virus and its host. Furthermore, it provides the first catalogue of alternative splicing events found in primary human CD4(+) T cells productively infected with HIV-1

UNE APPROCHE MULTIMODALE POUR ACCOMPAGNER LA LECTURE LITTÉRAIRE AU SECONDAIRE : CRÉER DES BANDES-ANNONCES À PARTIR DE BANDES DESSINÉES

Le problème à l’origine de notre recherche est lié à l’utilisation de la bande dessinée en classe de français au secondaire. Même si de récentes recherches démontrent que la bande dessinée constitue une forme littéraire signifiante et stimulante pour les jeunes (Boutin, 2010; Grondin, Boutin, Gendron, Martel et Beaudoin, 2011; Lebrun, 2004), celle-ci est encore le parent pauvre de l’enseignement de la lecture littéraire (Rouvière, 2012). Cette méconnaissance prive souvent les enseignants et les élèves de stratégies pour accompagner la lecture des BD et pour exploiter pleinement son potentiel langagier. Ainsi, il apparait essentiel de proposer de nouveaux dispositifs didactiques inspirés des assises théoriques de la littératie médiatique multimodale, de la lecture littéraire et du sujet lecteur. Nous présentons des résultats tirés d’une séquence didactique dans laquelle les élèves sont amenés à réaliser des bandes-annonces à partir de BD. Notre analyse des productions d’élèves montre que ces derniers se révèlent être des sujets multimodaux qui combinent la lecture, l’écriture, l’illustration, l’image filmée et la musique (Gee, 2008). Cette démarche nous permet également d’observer leur appropriation des œuvres notamment par le biais de leurs interprétations, de leurs transpositions dans des bandes-annonces et des apprentissages qu’ils ont réalisés.The problem at the beginning of our study is related to the use of graphic novels in french class in high school in Québec. Indeed, although recent research shows that graphic novels are a meaningful and stimulating literary form for students (Boutin, 2010; Grondin, Boutin, Gendron, Martel and Beaudoin, 2011; Lebrun, 2004), it is still the weak link of literature and further regarding the teaching of literary reading (Rouviere, 2012). This lack of knowledge often deprives teachers and students of strategies to support the use of comics and graphic novels in school and to fully exploit its language potential. So, it appears essential to propose new teaching devices to use this literary form in the classroom. Guided by the theoretical foundations of the multimodal media literacy, literary reading and the reader, we present results from a teaching sequence in which students are asked to create trailers from comics and graphic novels. Our analysis of students productions shows that they appear to be multimodal subjects that combine reading, writing, illustration, filmed image and music (Gee, 2008). This approach also allows us to observe their appropriation of works including through their interpretations, their transpositions in trailers and learning they have made

Jean-Pierre Séguin : Portraits, 1976-2006

The overall theme for the 4th Biennial International Network of Indigenous Health Knowledge and Development (INIHKD)Conference was ‘Knowing Our Roots: Indigenous Medicines, Health Knowledges and Best Practices’. Conference activities were grouped around the following broad themes:\ud \ud •Building of Indigenous research capacity, partnerships and workforce;\ud •Sharing of innovative, traditional and contemporary Indigenous knowledges, especially with respect to culturally-grounded interventions and evidenced-based “best and promising practices”; \ud •Identification of successful Indigenous health policy solutions; and \ud •Sharing of ethical, Indigenous-based research protocols and methodologies.\ud \ud This keynote plenary presentation focused on 'best practice' in research asking the questions: \ud \ud What kind of research will I do? \ud What kind of research will I be?\ud What is the contribution that I will make?\ud what will be my legacy?\ud \ud \u

Transcriptomic profile of mock-infected, uninfected bystander and HIV-1-infected cells.

<p>A) Volcano plots from the limma analysis of the transcriptome of cells fractions described in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002861#ppat-1002861-g001" target="_blank">Figure 1D</a>, at 1% FDR and 1.7 fold-change cut-off (represented by lines). The log10 of the p-value adjusted for multiple comparisons (Benjamini and Hochberg) is used for the Y axis and the log2 of the fold change is used for the X axis. Left columns: comparison between mock-infected versus uninfected bystander cell populations shows no statistically significant genes passing both thresholds at any time point or in aggregate analysis (labelled “all”). Center columns: comparison between mock-infected and virus-infected cells. Right columns: comparison between uninfected bystander and HIV-1-infected cells. B) Proportional Venn diagrams of above data, illustrating the overlap of DEGs at 24, 48 and 72 h for mock vs infected and bystander vs infected comparisons. C) Unsupervised hierarchical clustering (per sample and per gene) of differentially-expressed genes in the dataset. The similarity between mock-infected and uninfected bystander cells is obvious. Moreover, HIV-1-infected cell samples cluster together at the 24 h time point, but diverge on a per-sample basis at 48 and 72 h, illustrating that, although a common subset of T cells are infected early on, the precise context preferred by the virus can evolve differently over time on a per-sample basis.</p

Gene Ontology overrepresentation analysis of genes differentially expressed in HIV-1-infected cells.

<p>Unsupervised hierarchical clustering (per gene) of statistically over-represented Gene Ontology & KEGG pathway categories according to DAVID analysis. Since the first three categories (Immune system process – p = 1.9×10⁻¹⁷, Cytokine-cytokine receptor interaction – p 1×10⁻²⁹, Regulation of leukocyte activation – p = 1.4×10⁻⁹) overlap significantly, they are presented as a single cluster. Positive and negative regulation of apoptosis (p = 5.8×10⁻⁷ and 6×10⁻⁶, respectively) are both part of the Regulation of apoptosis category, but are here presented separately to better illustrate the absence of trend, in either direction. FOS/JUN (p = 2.3×10⁻⁵), the p53 pathway (p = 2.2×10⁻⁶) and Map kinase phosphatase (p = 2.3×10⁻⁵) are also identified as being over-represented and have implication for HIV-1 biology. All p-values mentioned above are corrected for multiple testing according to Bonferroni. The same color scale as <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002861#ppat-1002861-g002" target="_blank">Figure 2</a> applies.</p

Bibliography analysis and focus on neglected genes.

<p>A) Co-citation analysis was performed with Bibliosphere and exported to Gephi. The data shown is from the HIV-1-infected versus uninfected bystander cells comparison at the 24 h time point. Pairs of genes with at least three abstracts co-citing the genes at the sentence level were considered as significant. Red genes are over-expressed in virus-infected cells while blue genes are under-expressed. The size of circles is inversely correlated to the corrected p-value obtained in the experiment (i.e. the bigger the circle, the smaller the p-value). The length of links between nodes is inversely correlated with the number of abstracts found in Pubmed for the two related genes. Gephi allows dynamic filtering and interaction with the data. Readers are encouraged to download Gephi (<a href="http://gephi.org" target="_blank">http://gephi.org</a>) and use the graph file (Dataset S2) to explore the dataset dynamically. Poorly studied genes having no significant relationship with other members are shown in the right portion of the graph. B) Hierarchical clustering of gene categories (Kruppel associated box – p = 3.7×10⁻³ and GTPase regulator activity – p = 8.3×10⁻⁴) identified as being statistically over-represented among understudied genes.</p