Interplay between HIV and microRNAs in AIDS-related lymphomas

Infectious Agents and Cancer, 2014

Background: A close association between HIV infection and the development of cancer exists. Although the advent of highly active antiretroviral therapy has changed the epidemiology of AIDS-associated malignancies, a better understanding on how HIV can induce malignant transformation will help the development of novel therapeutic agents.

Genes & …, 1997

Specific inhibitors of histone deacetylase, such as trichostatin A (TSA) and trapoxin (TPX), are potent inducers of HIV-1 transcription in latently infected T-cell lines. Activation of the integrated HIV-1 promoter is accompanied by the loss or rearrangement of a positioned nucleosome (nuc-1) near the viral RNA start site. Here we show that TSA strongly induces HIV-1 transcription on chromatin in vitro, concomitant with an enhancer factor-assisted increase in the level of acetylated histone H4. TSA treatment, however, did not detectably alter enhancer factor binding or the positioning of nuc-1 on the majority of the chromatin templates indicating that protein acetylation and chromatin remodeling may be limiting steps that occur only on transcriptionally competent templates, or that remodeling of nuc-1 requires additional factors. To assess the number of active chromatin templates in vitro, transcription was limited to a single round with low levels of the detergent Sarkosyl. Remarkably, HIV-1 transcription on chromatin was found to arise from a small number of active templates that can each support nearly 100 rounds of transcription, and TSA increased the number of active templates in each round. In contrast, transcription on naked DNA was limited to only a few rounds and was not responsive to TSA. We conclude that HIV-1 enhancer complexes greatly facilitate transcription reinitiation on chromatin in vitro, and act at a limiting step to promote the acetylation of histones or other transcription factors required for HIV-1 enhancer activity.

Genes, 2021

Viruses and viral components have been shown to manipulate the expression of host microRNAs (miRNAs) to their advantage, and in some cases to play essential roles in cancer pathogenesis. Burkitt lymphoma (BL), a highly aggressive B-cell derived cancer, is significantly over-represented among people infected with HIV. This study adds to accumulating evidence demonstrating that the virus plays a direct role in promoting oncogenesis. A custom miRNA PCR was used to identify 32 miRNAs that were differently expressed in Burkitt lymphoma cells exposed to HIV-1, with a majority of these being associated with oncogenic processes. Of those, hsa-miR-200c-3p, a miRNA that plays a crucial role in cancer cell migration, was found to be significantly downregulated in both the array and in single-tube validation assays. Using an in vitro transwell system we found that this downregulation correlated with significantly enhanced migration of BL cells exposed to HIV-1. Furthermore, the expression of th...

Immunobiology, 1997

Regulation of transcription is a key feature of the HIV-1 life cycle. 'In recent years, various sequence elements and transcription factors have been shown to participate in HIV-1 transcription control. New evidence, however, has shown that chromatin organization plays a key role in the establishment of a transcriptionally regulated HIV-1 LTR. The present review discusses recent data obtained on reconstituted and genomic HIV-1 chromatin templates. The transcription regulatory unit contained in the HIV-l LTR is probably the RNA polymerase II-dependent promoter which attracted the most attention from investigators in the last decade. Every step of HIV-l life cycle is a potential target for inhibiting the outbreak of AIDS. Downregulation of this promoter by extracellular signals or drugs could be an approach to prevent viral replication. Until the early nineties, the molecular mechanisms occuring at the HIV-l LTR were examined essentially by now conventional gene expression methodologies, including transient transfections in cell lines and in vitro transcription assays. A large number of studies led to the characterization of various transcription factor binding sites in the LTR which appear important for viral propagation (reviewed in 1, 2). However, recent investigations on reconstituted chromatin and on the integrated provirus suggest that the mechanisms of HIV-l transcription regulation ar:~ore complex than the somewhat simple models derived from transient transcnpuon assays. Evolution has devised the transcriptional machinery to work on the complex chromatin template found in intact cells. The characterization of various activities that can modulate chromatin organization provided some of the major advances in our understanding of eukaryotic transcription during these last years. Studies in yeast and Drosophila have identified genes involved in repres-Abbreviations: AIDS = aquired immunodeficiency syndrome; DHS = DNase! hypersensitive site; DMS = dimethylsulfate; HAT = histone acetyltransferase; HIV-l = human immunodeficiency virus type 1; IL-2 = interleukin 2; 1ST = inducer of short transcripts; LTR = long terminal repeat; MMTV = mouse mammary tumor virus; PMA = phorbol-12-myristate-13-acetate;

Journal of Biological Chemistry, 2003

2013

We thank the reviewers for their time and effort in reviewing our manuscript and offer valuable suggestions. We have revised the manuscript accordingly and addressed the concerns. Revised text is highlighted in the revised manuscript. Reviewer 2: The authors indicate that gene expression is significantly altered in PBMCs in response to virus replication; interestingly the infected individuals, with low or undetectable viral load, exhibit a gene expression profile very similar to control or uninfected subjects. As regards this point, the authors should better explain the status of the uninfected subjects. Are these subjects HIV-1 exposed uninfected? Response: Based on the information gathered none of the subjects except one are exposed to HIV-1 or considered as HESN. Eliminating that specific subject from our analysis did not make a difference.

Enunciados consolidados do Fórum Permanente de Processualistas Civis (FPPC) sobre o CPC-2105: Salvador, Rio de Janeiro, Belo Horizonte, Vitória e Curitiba

Ejercicio Práctico UNIDAD TEMÁTICA 8 Cómo trabajar con el costeo ABC 1-Identificar los datos a. Costos fijos indirectos (por áreas o sectores -centros de costos) b. Actividades principales (por área generalmente -centros de costos) c. Uso de la estructura de los sectores c. Datos globales (estándares o históricos) que reflejan los niveles de actividad con los que trabaja la empresa 2-Pasos para la resolución de un caso a. Calcular los costos fijos mensuales por actividad (CFM actividad ) Costeo basado en actividades Costeo basado en actividades Ejercicio Práctico UNIDAD TEMÁTICA 8 Cómo trabajar con los CFI bajo el costeo ABC 1-Identificar los datos a. Costos fijos indirectos (por áreas o sectores -centros de costos) b. Actividades principales (por área generalmente -centros de costos) c. Uso de la estructura de los sectores c. Datos globales (estándares o históricos) que reflejan los niveles de actividad con los que trabaja la empresa 2-Pasos para la resolución de un caso a. Calcular los costos fijos mensuales por actividad (CFM actividad ) b. Determinar el inductor de cada actividad Se deberá identificar qué tipo de actividad es y qué "unidad de medida" mejor identifica la causa de costo de esa actividad. Costeo basado en actividades Costeo basado en actividades Ejercicio Práctico UNIDAD TEMÁTICA 8 Cómo trabajar con los CFI bajo el costeo ABC 1-Identificar los datos a. Costos fijos indirectos (por áreas o sectores -centros de costos) b. Actividades principales (por área generalmente -centros de costos) c. Uso de la estructura de los sectores c. Datos globales (estándares o históricos) que reflejan los niveles de actividad con los que trabaja la empresa