HIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signaling

Cheng, Sherman M.; Li, J.; Lin, San San; Lee, Davy C. W.; Liu, Li; Chen, Zhiwei; Lau, Alan F.

doi:10.1182/blood-2008-10-183525

Cited by 42 publications

(32 citation statements)

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“…Furthermore, HIV-1 Tat-induced SOCS2 has also been reported to inhibit IFN-␥ signaling in monocytes (10). Cheng et al recently showed that HIV-1 Tat is sufficient to dampen both STAT1 activation and downstream target gene expression in response to IFN-␥ but that this protective immune response is restored following knockdown of SOCS2 (10). Although the authors of this study did not evaluate the effect of Tat-induced SOCS2 on pathogen clearance, these data suggest that multiple HIV-1-induced SOCS proteins may promote secondary infections by inhibiting the antipathogenic effects of IFN-␥.…”

Section: Effects Of Socs Expression On Viral Diseasementioning

confidence: 67%

“…These studies suggest that HIV-1 Tat-induced SOCS3 disrupts protective type I IFN signaling within macrophages, allowing for enhanced viral replication and viral pathogenesis. HIV-1 Tat has also been shown to attenuate type II IFN signaling in human monocytes in a SOCS2-dependent manner (10). This finding has significant implications for protection from bacte- VOL.…”

Section: Virally Exploited Functions Of Socs Proteinsmentioning

confidence: 99%

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Viral Exploitation of Host SOCS Protein Functions

Akhtar

Benveniste

2011

J Virol

110

102

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Over the past decade, a family of host proteins known as suppressors of cytokine signaling (SOCS) have emerged as frequent targets of viral exploitation. Under physiologic circumstances, SOCS proteins negatively regulate inflammatory signaling pathways by facilitating ubiquitination and proteosomal degradation of pathway machinery. Their expression is tightly regulated to prevent excessive inflammation while maintaining protective antipathogenic responses. Numerous viruses, however, have developed mechanisms to induce robust host SOCS protein expression following infection, essentially "hijacking" SOCS function to promote virus survival. To date, SOCS proteins have been shown to inhibit protective antiviral signaling pathways, allowing viruses to evade the host immune response, and to ubiquitinate viral proteins, facilitating intracellular viral trafficking and progeny virus assembly. Importantly, manipulation of SOCS proteins not only facilitates progression of the viral life cycle but also powerfully shapes the presentation of viral disease. SOCS proteins can define host susceptibility to infection, contribute to peripheral disease manifestations such as immune dysfunction and cancer, and even modify the efficacy of therapeutic interventions. Looking toward the future, it is clear that a better understanding of the role of SOCS proteins in viral diseases will be essential in our struggle to modulate and even eliminate the pathogenic effects of viruses on the host.

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Section: Effects Of Socs Expression On Viral Diseasementioning

confidence: 67%

Section: Virally Exploited Functions Of Socs Proteinsmentioning

confidence: 99%

Viral Exploitation of Host SOCS Protein Functions

Akhtar

Benveniste

2011

J Virol

110

102

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“…Treatment of cells with recombinant Tat has been suggested to suppress IFNγ signaling through upregulation of SOCS2 [63] and Tat has been reported to interact with PKR, modulating its function [64]. Expression of Tat in dendritic cells leads to induction of interferon-inducible genes encoding T cell chemo-attractants, luring these target cells to sites of infection [36].…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus Tat associates with a specific set of cellular RNAs

et al. 2014

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BackgroundHuman Immunodeficiency Virus 1 (HIV-1) exhibits a wide range of interactions with the host cell but whether viral proteins interact with cellular RNA is not clear. A candidate interacting factor is the trans-activator of transcription (Tat) protein. Tat is required for expression of virus genes but activates transcription through an unusual mechanism; binding to an RNA stem-loop, the transactivation response element (TAR), with the host elongation factor P-TEFb. HIV-1 Tat has also been shown to alter the expression of host genes during infection, contributing to viral pathogenesis but, whether Tat also interacts with cellular RNAs is unknown.ResultsUsing RNA immunoprecipitation coupled with microarray analysis, we have discovered that HIV-1 Tat is associated with a specific set of human mRNAs in T cells. mRNAs bound by Tat share a stem-loop structural element and encode proteins with common biological roles. In contrast, we do not find evidence that Tat associates with microRNAs or the RNA-induced silencing complex (RISC). The interaction of Tat with cellular RNA requires an intact RNA binding domain and Tat RNA binding is linked to an increase in RNA abundance in cell lines and during infection of primary CD4+ T cells by HIV.ConclusionsWe conclude that Tat interacts with a specific set of human mRNAs in T cells, many of which show changes in abundance in response to Tat and HIV infection. This work uncovers a previously unrecognised interaction between HIV and its host that may contribute to viral alteration of the host cellular environment.

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“…Socs1 and Socs3 also have the additional kinase inhibitory region (KIR) and extended SH2 motif (ESS) upstream of SH2 domain, which are absent in other SOCS members (Piessevaux et al 2008b). SOCS proteins are widely expressed at tissue level (Delgado-Ortega et al 2011), and their production can be induced by microbial/ viral infection or by cytokine treatment (Hebenstreit et al 2003, Cheng et al 2009). At cellular level, SOCS expression is well documented to serve as the feedback repressor for cytokine signaling via inhibition of JAK/ STAT pathway (Croker et al 2008) and plays a protective role in preventing hyperactivation of immune system, which can lead to autoimmune/inflammatory disorders (Liang et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

Jiang

Jia

et al. 2016

Journal of Endocrinology

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Type II suppressor of cytokine signaling (SOCS) serve as feedback repressors for cytokines and are known to inhibit growth hormone (GH) actions. However, direct evidence for SOCS modulation of GH-induced insulin-like growth factor 1 (Igf1) expression is lacking, and the post-receptor signaling for SOCS expression at the hepatic level is still unclear. To shed light on the comparative aspects of SOCS in GH functions, grass carp was used as a model to study the role of type II SOCS in GH-induced Igf1 expression. Structural identity of type II SOCS, Socs1-3 and cytokine-inducible SH2-containing protein (Cish), was established in grass carp by 5'/3'-RACE, and their expression at both transcript and protein levels were confirmed in the liver by RT-PCR and LC/MS/MS respectively. In carp hepatocytes, GH treatment induced rapid phosphorylation of JAK 2 , STATs, MAPK, PI3K, and protein kinase B (Akt) with parallel rises in socs1-3 and cish mRNA levels, and these stimulatory effects on type II SOCS were shown to occur before the gradual loss of igf1 gene expression caused by prolonged exposure of GH. Furthermore, GH-induced type II SOCS gene expression could be negated by inhibiting JAK 2 , STATs, MEK 1/2 , P 38 MAPK , PI3K, and/or Akt respectively. In CHO cells transfected with carp GH receptor, over-expression of these newly cloned type II SOCS not only suppressed JAK 2 /STAT 5 signaling with GH treatment but also inhibited GH-induced grass carp Igf1 promoter activity. These results, taken together, suggest that type II SOCS could be induced by GH in the carp liver via JAK 2 /STATs, MAPK, and PI3K/Akt cascades and serve as feedback repressors for GH signaling and induction of igf1 gene expression.

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HIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signaling

Cited by 42 publications

References 50 publications

Viral Exploitation of Host SOCS Protein Functions

Viral Exploitation of Host SOCS Protein Functions

Human immunodeficiency virus Tat associates with a specific set of cellular RNAs

Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes

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