Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile

ABSTRACT Primary effusion lymphomas (PELs) are specifically associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection and most frequently occur in human immunodeficiency virus (HIV)-positive individuals as lymphomatous effusions in the serous cavities without a detectable solid tumor mass. Most PELs have concomitant Epstein-Barr virus (EBV) infection, suggesting that EBV is an important pathogenetic cofactor, although other as yet unidentified cofactors, such as cellular genetic alterations, are also likely to play a role. Lymphomatous effusions that lack KSHV also occur; these are frequently EBV associated in the setting of HIV infection. Here we used gene expression profile analysis to determine the viral impact on cellular gene expression and the pathogenesis of these lymphomatous effusions. Our results show that many genes, including cell cycle and signal transduction regulators, are differentially expressed between KSHV-positive PELs and KSHV-negative lymphomatous effusions and also between KSHV-positive, EBV-positive and KSHV-positive, EBV-negative PELs. Our results confirm that KSHV plays an important role in the pathogenesis of PELs, as its presence selects for a very distinct cellular gene expression category and a clearly different lymphoma type. Within the KSHV-positive PELs, the effect of EBV is more subtle but nevertheless clear.

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Bioinformatics: Human Gene Expression Profile after Respiratory Syncytial Virus Infection

Asian Journal of Epidemiology ◽

10.3923/aje.2019.38.44 ◽

2019 ◽

Vol 12 (2) ◽

pp. 38-44

Author(s):

Abdulrhem Thonnon AL-Ghazal ◽

Manar Fawzi Altaee

Keyword(s):

Gene Expression ◽

Respiratory Syncytial Virus ◽

Virus Infection ◽

Gene Expression Profile ◽

Respiratory Syncytial Virus Infection ◽

Expression Profile ◽

Human Gene ◽

Human Gene Expression ◽

Syncytial Virus

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Epstein-Barr Virus Related Classical Hodgkin Lymphoma Reveals a Pro-Inflammatory RNA Expression Profile at Diagnosis

Blood ◽

10.1182/blood.v128.22.5292.5292 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5292-5292

Author(s):

Priscilla Brito Silva ◽

Juliana Monte Real ◽

Ludmila Rodrigues Pinto Ferreira ◽

Adriana M. Damasco Penna ◽

Gustavo Henrique Esteves ◽

...

Keyword(s):

Gene Expression ◽

Hodgkin Lymphoma ◽

Expression Profile ◽

Epstein Barr Virus ◽

Immune Gene ◽

Classical Hodgkin Lymphoma ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

Inflammatory Profile

Abstract Introduction: Epstein-Barr virus (EBV) is associated with a variety of human diseases including classical Hodgkin lymphoma. EBV recruit mainly cells with anti-inflammatory properties, providing an immunosuppressive environment and the immune escape of Reed-Sternberg (RS) cells. Studies have shown that patients with cHL EBV-related is associated with increased gene expression of IL-6, IL-10 and CD25. However, the molecular mechanism by which EBV orchestrates the cytokines secretion profile that promotes microenvironment propitious to survival and growth to neoplastic RS cells remains unclear. Objectives: In this study we aimed evaluate the immune gene expression profile and association in EBV-related cHL patients. Methods: This is an open multicenter study and, so far, we included 51 patients consecutively from February 2011 to November 2015. Twenty consecutively diagnosed cHL patients, with whole blood RNA extracted at diagnosis and after treatment (1 to 4 months), were recruited for this study and prospectively evaluated. The general expression of 96 messengers RNAs present in the peripheral blood and involved in immune response was performed by a customized quantitative real-time PCR array (TaqMan¨Low Density Array). We also included 7 healthy controls. The data was normalized with B2M mRNAs levels and relative gene expression was calculated by the 2^DDCt method, considering Wilcoxon test and Benjamini-Hochberg adjustment to correct p-values. In this study, only cHL patients whose histology could be confirmed were studied. The EBV status was evaluated in paraffin-embedded tissue by immunohistochemical analysis. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results: From the 20 patients recruited for this study, 12 (60%) were male, 18 (90%) patients presented with B symptoms and 19 (95%) patients had advanced diseases at diagnosis (stage IIBx, II and IV). Interestingly, 5 (31%) had Epstein-Barr virus related cHL. The EBV infection reflected in increased amounts of IL-2 (8 fold, p=0.040), IL-23A (2.4 fold, p=0.040) and IL-7 (3.4 fold, p=0.053) mRNAs in blood circulation at the time of diagnosis (summarized in following table). After treatment, no mRNA immune gene was different expressed, suggesting that it returned to normal levels in both groups. We not found any correlation with clinical and epidemiological features and EBV. Conclusions: In this study, we showed that, EBV infection in patients with cHL is related with pro-inflammatory profile gene expression. Although IL-2 and IL-7 are related with a pro-inflammatory profile, these cytokines are co-stimulators of a standard immune suppression as their receptors are markers of regulatory T cells (IL7-R= CD127 and IL-2Ra= CD25). IL-2/IL-2Ra and IL-7/IL-7R constitutes an additional signaling pathway between H-RS cells and their reactive cellular background, thereby affecting proliferation and survival of tumor cells, acting as a cofactor for Tregs expansion and EBV infection. Certainly our results need to be validated in larger cohorts. Nevertheless, given the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones, we emphasize the importance of our results. Table Table. Disclosures No relevant conflicts of interest to declare.

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KnockTF: a comprehensive human gene expression profile database with knockdown/knockout of transcription factors

Nucleic Acids Research ◽

10.1093/nar/gkz881 ◽

2019 ◽

Vol 48 (D1) ◽

pp. D93-D100 ◽

Cited By ~ 6

Author(s):

Chenchen Feng ◽

Chao Song ◽

Yuejuan Liu ◽

Fengcui Qian ◽

Yu Gao ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Gene Expression Profile ◽

Expression Profile ◽

Target Genes ◽

Human Gene ◽

Biological Effects ◽

Tissue Cell ◽

Human Gene Expression ◽

Network Analyses

Abstract Transcription factors (TFs) and their target genes have important functions in human diseases and biological processes. Gene expression profile analysis before and after knockdown or knockout is one of the most important strategies for obtaining target genes of TFs and exploring TF functions. Human gene expression profile datasets with TF knockdown and knockout are accumulating rapidly. Based on the urgent need to comprehensively and effectively collect and process these data, we developed KnockTF (http://www.licpathway.net/KnockTF/index.html), a comprehensive human gene expression profile database of TF knockdown and knockout. KnockTF provides a number of resources for human gene expression profile datasets associated with TF knockdown and knockout and annotates TFs and their target genes in a tissue/cell type-specific manner. The current version of KnockTF has 570 manually curated RNA-seq and microarray datasets associated with 308 TFs disrupted by different knockdown and knockout techniques and across multiple tissue/cell types. KnockTF collects upstream pathway information of TFs and functional annotation results of downstream target genes. It provides details about TFs binding to promoters, super-enhancers and typical enhancers of target genes. KnockTF constructs a TF-differentially expressed gene network and performs network analyses for genes of interest. KnockTF will help elucidate TF-related functions and potential biological effects.

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