Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals

Fuente, Cynthia de la; Santiago, Francisco; Deng, Longwen; Eadie, Carolyne; Zilberman, Irene; Kehn, Kylene; Maddukuri, Anil; Baylor, Shanese; Wu, Kaili; Lee, Chee Gun; Pumfery, Anne; Kashanchi, Fatah

doi:10.1186/1471-2091-3-14

Cited by 74 publications

(12 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The third group of gene sets that is usually modulate by virus is the host cell transcription apparatus [31]. By providing direct gene pattern, our results confirmed that this strategy was also exploited both in the HIV mono- and HCV/HIV co-infected individuals.…”

Section: Discussionsupporting

confidence: 72%

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

Liu

Zhao

Lü

et al. 2014

Virol J

View full text Add to dashboard Cite

BackgroundBecause of the shared transmission routes, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HIV) is very common. Accumulated clinical evidence showed that one could alter the infectious course of the other virus in HIV and HCV co-infected individuals. However, little is known on the molecular basis of HIV/HCV interactions and their modulations on hosts.MethodsIn this study, treatment-naive HIV, HCV mono-/co-infected individuals with CD4+ T cell counts >300/μl were recruited and their gene expression profiles were investigated by microarray assays. The differentially expressed genes were identified and validated by quantitative real-time PCR (qRT-PCR). To further understand the biological meanings of the gene expression profiles in these three groups, GSEA analysis (version 2.0, Broad Institute http://www.broad.mit.edu/gsea) was performed.ResultsBy gene set enrichment analysis, we revealed that gene sets of cell cycle progression, innate immune response and some transcription factors in CD4+ T cells were mainly affected by HIV; while genes associated with GPCR signaling were the major targets of HCV. Metabolic pathways were modulated by both HCV and HIV viruses.ConclusionsThis study for the first time offers gene profiling basis for HCV/HIV mono-/co- infections in human beings. HIV infection displayed the great impact on transcription profile of CD4+ T cells in HIV/HCV co-infected individuals. Genes related to cell cycle arrest were significantly mediated by HIV which may lead to dysfunction of CD4+ T cells and acceleration of HCV-related disease progression in the co-infections.

show abstract

Section: Discussionsupporting

confidence: 72%

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

Liu

Zhao

Lü

et al. 2014

Virol J

View full text Add to dashboard Cite

show abstract

“…Thus, we took advantage of this marker to perform, for the first time, comparative genomic profiling of primary latently infected resting memory CD4 ϩ T cells versus their uninfected counterparts sorted from the same culture. Previous studies were carried out with latently infected cell lines (55)(56)(57), but no studies using primary CD4 ϩ T cells have been reported. Krishnan et al showed altered expression levels of genes encoding components of the proteasome, histone deacetylases, and transcription factors in the chronically infected cell lines ACH-2, J1.1, and U1 compared to the parental uninfected cell lines A3.01, Jurkat, and U937 (56).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, our microarray study indicated that in latently infected cells, gene programs were modulated in a way that is consistent with cell quiescence, cell survival, transcription silencing, and evasion of the immune system. Since HIV-1 proteins have a profound effect on many host cell functions that are relevant to its life cycle (55,58,(62)(63)(64)(65)(66)(67)(68)(69), it is conceivable that they might also affect cell functions relevant to latency. On the other hand, it is possible to speculate that a subset of CD4 ϩ T cells with a gene expression profile similar to the one emerging from our microarray analysis already preexists in peripheral blood of healthy individuals, so that upon HIV-1 infection, it provides an ideal environment for the establishment of latency.…”

Section: Discussionmentioning

confidence: 99%

High Levels of CD2 Expression Identify HIV-1 Latently Infected Resting Memory CD4⁺T Cells in Virally Suppressed Subjects

Iglesias-Ussel

Vandergeeten

Marchionni

et al. 2013

J Virol

View full text Add to dashboard Cite

c Resting memory CD4؉ T cells are the largest reservoir of persistent infection in HIV-1-positive subjects. They harbor dormant, stably integrated virus despite suppressive antiretroviral therapy, posing an obstacle to a cure. Surface markers that identify latently infected cells remain unknown. Microarray analyses comparing resting latently infected and uninfected CD4 ؉ T cells generated in vitro showed profound differences in the expression of gene programs related to transcriptional and posttranscriptional regulation, cell proliferation, survival, cycle progression, and basic metabolism, suggesting that multiple biochemical and metabolic blocks contribute to preventing viral production in latently infected cells. We identified 33 transcripts encoding cell surface markers that are differentially expressed between latently infected and uninfected cells. Quantitative reverse transcriptase PCR (RT-QPCR) and flow cytometry analyses confirmed that the surface marker CD2 was expressed at higher levels on latently infected cells. To validate this result in vivo, we sorted resting memory CD4 ؉ T cells expressing high and low surface levels of CD2 from six HIV-1-infected subjects successfully treated with antiretroviral drugs for at least 3 years. Resting memory CD4 ؉ CD2high T cells from all subjects harbored higher HIV-1 DNA copy numbers than all other CD4 ؉ T cell subsets. Moreover, after ex vivo viral reactivation, robust viral RNA production was detected only from resting memory CD4 ؉ CD2 high T cells but not from other cell subsets. Altogether, these results show that a high CD2 expression level is a hallmark of latently infected resting memory CD4 ؉ T cells in vivo.

show abstract

“…In addition to its role in the HIV-1 life cycle, Tat has the ability to influence a cell's phenotype by modulating the expression of cellular genes [6,7]. The protein has been found to stimulate the expression of immuno-regulatory cytokines, including the production of IL-6, the dysregulation of which is implicated in the pathogenesis of several AIDS-associated pathologies such as psoriasis, B cell lymphoma and Kaposi's sarcoma [8].…”

Section: Introductionmentioning

confidence: 98%

HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

et al. 2009

View full text Add to dashboard Cite

HIV infection results in severe immune dysfunction with ensuing sequelae that includes characteristic opportunistic infections. Pneumocystis pneumonia (PCP) is one of the most common of these infections and is routinely treated with sulphamethaxazole (SMX). Although this drug is known to cause hypersensitivity adverse drug reactions (ADRs) in 0.1% of the general population, the incidence of these ADRs increases tenfold in the HIV-positive population. The HIV-1 trans-activator of transcription (HIV-1 Tat) together with the drug metabolite sulphamethaxazole-hydroxylamine (SMX-HA) have both been reported to be factors in these hypersensitivity ADRs. In this study, we use an inducible, Tat-expressing vector system to show that the level of Tat expression contributes to the cellular sensitivity of Jurkat T cells to SMX-HA. We further demonstrated that apoptosis is the likely mechanism by which this occurs. Thus, our data provide insight into the significant increase of SMX-related ADRs during the transition between HIV-1 infection and AIDS.

show abstract

Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals

Cited by 74 publications

References 105 publications

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

High Levels of CD2 Expression Identify HIV-1 Latently Infected Resting Memory CD4⁺T Cells in Virally Suppressed Subjects

HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

Contact Info

Product

Resources

About

Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals

Cited by 74 publications

References 105 publications

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

Gene expression profiling of CD4+T cells in treatment-naive HIV, HCV mono- or co-infected Chinese

High Levels of CD2 Expression Identify HIV-1 Latently Infected Resting Memory CD4+T Cells in Virally Suppressed Subjects

HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

Contact Info

Product

Resources

About

High Levels of CD2 Expression Identify HIV-1 Latently Infected Resting Memory CD4⁺T Cells in Virally Suppressed Subjects