Post-transcriptional control of the interferon system

Khabar, Khalid S.A.; Young, Howard A.

doi:10.1016/j.biochi.2007.02.008

Cited by 74 publications

(69 citation statements)

References 88 publications

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“…T he interferon (IFN) response plays an important role in innate immunity to viruses (1,2). Many cell types produce IFN in response to a viral invasion, and IFN acts on neighboring healthy cells to ward off further viral attack.…”

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confidence: 99%

Human Cytokinome Analysis for Interferon Response

Al-Yahya

Mahmoud

Al-Zoghaibi

et al. 2015

J Virol

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IMPORTANCE Innate immunity to viruses is an early defense system to ward off viruses. One mediator is interferon (IFN), which activates a cascade of biochemical events that aim to control the virus life cycle. In our work, we examined more than 200 cytokines, soluble mediators produced within the body as a result of infection, for the ability to enhance IFN action. We identified enhanced interactions with specific IFNs and cytokines. We also revealed that betacellulin, IL-17, and IL-11 cytokines have the novel property of enhancing the antiviral action of IFN against several viruses. These results demonstrate that the human genome codes for previously unknown proteins with unrelated functions that can augment the innate immunity to viruses. Knowing these interactions not only helps our understanding of immunity to viruses and emerging diseases, but can also lead to devising possible new therapeutics by enhancing the mediator of antiviral action itself, IFN.

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mentioning

confidence: 99%

Human Cytokinome Analysis for Interferon Response

Al-Yahya

Mahmoud

Al-Zoghaibi

et al. 2015

J Virol

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“…Although transcriptional regulation of IFN gene expression in the activation of the antiviral innate immune response has been well characterized, the inherent instability of type I IFN mRNAs indicates that posttranscriptional regulation also contributes to the antiviral immune response (20). To date, much of the emphasis on the contribution of mRNA turnover within the immune response has focused on AU-rich element (ARE)-mediated mRNA decay of cytokine and chemokine mRNAs possessing AREs within their 3= untranslated regions (UTRs) (32).…”

mentioning

confidence: 99%

Dcp2 Decapping Protein Modulates mRNA Stability of the Critical Interferon Regulatory Factor (IRF) IRF-7

Dai

Song

et al. 2012

Molecular and Cellular Biology

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bThe mammalian Dcp2 mRNA-decapping protein functions primarily on a subset of mRNAs in a transcript-specific manner. Here we show that Dcp2 is an important modulator of genes involved in the type I interferon (IFN) response, which is the initial line of antiviral innate immune response elicited by a viral challenge. Mouse embryonic fibroblast cells with reduced Dcp2 levels (Dcp2 ␤/␤ ) contained significantly elevated levels of mRNAs encoding proteins involved in the type I IFN response. In particular, analysis of a key type I IFN transcription factor, IFN regulatory factor 7 (IRF-7), revealed an increase in both IRF-7 mRNA and protein in Dcp2 ␤/␤ cells. Importantly, the increase in IRF-7 mRNA within the background of reduced Dcp2 levels was attributed to a stabilization of the IRF-7 mRNA, suggesting that Dcp2 normally modulates IRF-7 mRNA stability. Moreover, Dcp2 expression was also induced upon viral infection, consistent with a role in attenuating the antiviral response by promoting IRF-7 mRNA degradation. The induction of Dcp2 levels following a viral challenge and the specificity of Dcp2 in targeting the decay of IRF-7 mRNA suggest that Dcp2 may negatively contribute to the innate immune response in a negative feedback mechanism to restore normal homeostasis following viral infection.

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“…Second, we tested whether regulation of interferonstimulated genes associated with inhibition of HIV-1 [17][18][19][20] was induced with NTZ as thiazolides have been shown to interfere with viral infection through activation of type I interferon-associated mechanisms. 13,21,22 We analyzed the modulation of two known type I interferon-induced negative regulators of viral replication (ABOBEC 3G and tetherin [23][24][25][26][27][28] ) following 48-h incubation of MDM with 10 lg/ml NTZ.…”

Section: Gekonge Bardin and Montanermentioning

confidence: 99%

Short Communication: Nitazoxanide Inhibits HIV Viral Replication in Monocyte-Derived Macrophages

Gekonge

Bardin

Montaner

2015

AIDS Research and Human Retroviruses

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We document the anti-HIV activity of nitazoxanide (NTZ), the first member of the thiazolide class of antiinfective drugs, originally effective against enteritis caused by Cryptosporidium parvum and Giardia lamblia. NTZ has been administered extensively worldwide, with no severe toxicities associated with its use. Here, we show for the first time that NTZ decreases HIV-1 replication in monocyte-derived macrophages (MDM) if present before or during HIV-1 infection. This NTZ effect is associated with downregulation of HIV-1 receptors CD4 and CCR5, and increasing gene expression of host cell anti-HIV resistance factors APOBEC3A/3G and tetherin. As NTZ is already in clinical use for other conditions, this newly described anti-HIV activity in MDM may facilitate innovative intensification strategies against HIV-1 when combined with current antiretroviral drug regimens.

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Post-transcriptional control of the interferon system

Cited by 74 publications

References 88 publications

Human Cytokinome Analysis for Interferon Response

Human Cytokinome Analysis for Interferon Response

Dcp2 Decapping Protein Modulates mRNA Stability of the Critical Interferon Regulatory Factor (IRF) IRF-7

Short Communication: Nitazoxanide Inhibits HIV Viral Replication in Monocyte-Derived Macrophages

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