Viruses, endoplasmic reticulum stress, and interferon responses

He, Bin

doi:10.1038/sj.cdd.4401833

Cited by 373 publications

(324 citation statements)

References 97 publications

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“…However, only three viral proteins, hepatitis C virus envelope E1/E2, herpes simplex virus ␥ 1 34.5, and human cytomegalovirus US11, have been shown to function as ER stress modifiers. The full extent of virus interaction with and manipulation of the ER stress response is not known (16). Our data show that KSHV responds to the UPR directly and therefore may reactivate under many different stress-inducing conditions.…”

Section: Discussionmentioning

confidence: 87%

X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation to KSHV Reactivation from Latency

Wilson¹,

Tsao²,

Webb³

et al. 2007

J Virol

102

130

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Reactivation of lytic replication from viral latency is a defining property of all herpesviruses. Despite this, the authentic physiological cues for the latent-lytic switch are unclear. Such cues should ensure that viral lytic replication occurs under physiological conditions, predominantly in sites which facilitate transmission to permissive uninfected cells and new susceptible hosts. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with the B-cell neoplasm primary effusion lymphoma (PEL), in which the virus remains latent. We have previously shown that PEL cells have the gene expression profile and immunophenotype of cycling preplasma cells (plasmablasts). Here, we show that the highly active spliced isoform of plasma cell transcription factor X box binding protein 1 (XBP-1s) is a lytic switch for KSHV. XBP-1s is normally absent in PEL, but the induction of endoplasmic reticulum stress leads to XBP-1s generation, plasma cell-like differentiation, and lytic reactivation of KSHV. XBP-1s binds to and activates the KSHV immediate-early gene ORF50 and synergizes with the ORF50 gene product RTA to induce a full lytic cycle. These data suggest that KSHV remains latent until B-cell terminal differentiation into plasma cells, the transcriptional environment of which provides the physiological "lytic switch" through XBP-1s. This links B-cell terminal differentiation to KSHV lytic reactivation.

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Section: Discussionmentioning

confidence: 87%

X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation to KSHV Reactivation from Latency

Wilson¹,

Tsao²,

Webb³

et al. 2007

J Virol

102

130

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show abstract

“…Most notably, tumors lack a well-developed blood supply, which, coupled with the rapid proliferation of tumor cells, leads to hypoxia, decreased glucose and amino acid supply, and low extracellular pH (5). Compounding these extrinsic noxae are tumor-intrinsic stressors, such as errors in the biosynthesis of glycoproteins and lipids (15,16), and viruses (17), which collectively induce ER stress.…”

Section: Er Stress and The Unfolded Protein Responsementioning

confidence: 99%

Tumor Stress Inside Out: Cell-Extrinsic Effects of the Unfolded Protein Response in Tumor Cells Modulate the Immunological Landscape of the Tumor Microenvironment

Mahadevan

Zanetti

2011

The Journal of Immunology

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The unfolded protein response (UPR) is a eukaryotic cellular adaptive mechanism that functions to cope with stress of the endoplasmic reticulum (ER). Accumulating evidence demonstrates that the tumor microenvironment contains stressors that elicit a UPR, which has been demonstrated to be a cell-intrinsic mechanism crucial for tumorigenesis. In addition, the UPR is a source of proinflammatory signaling whose downstream mediators may hamper antitumor immunity. We discuss how the UPR may impair Ag presentation, which could result in defective T cell priming, also leading to tumor escape and growth. Further, we discuss the recent finding that ER stress and attendant proinflammation can be transmitted from ER-stressed tumor cells to myeloid cells. The ideas presented suggest that, in addition to being a cell-intrinsic mechanism of tumor survival, the tumor UPR can serve as a cell-extrinsic regulator of tumorigenesis by remodeling the immune response in the tumor microenvironment.

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“…[5][6][7][8][9][10] In addition to the induction of IFNs, viral infections also trigger ER stress response. [11][12][13][14][15] A best-studied stress-responsive signaling pathway is the UPR. The UPR induces transmembrane stress sensors, IRE1, ATF6, and PERK, that are localized in the ER.…”

Section: Introductionmentioning

confidence: 99%

Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

Ishaq

Natarajan

2016

Signal Transduction Insights

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Supraphysiological concentrations (SPCs) of triiodo-l-thyronine (T3) have been used in the treatment of a number of nonviral diseases. However, the signaling mechanisms that regulate the function of T3 at these concentrations and their role in modulating cellular stress pathways and antiviral responses are unknown. Here, we have investigated the effects of SPCs of T3 on integrated stress response (ISR) signaling pathways and the replication of vesicular stomatitis virus (VSV). T3 amplified Poly IC-induced activation of RNA-dependent protein kinase, induced phosphorylation of eIF2α, stress granule (SG) formation, IRE1α phosphorylation, XBP1 splicing, and the expression of stress markers. T3 inhibited VSV replication by modulating SG formation and the expression of stress response markers. ISR activator guanabenz also inhibited VSV replication and amplified T3-induced anti-VSV response. To summarize, we have uncovered novel functions of T3 at SPCs as an activator of ISR signaling pathways and an inhibitor of VSV replication. This study offers a proof of principle of the concept that ISR activating agents like SPC of T3 and guanabenz can be potential antiviral agents.

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Viruses, endoplasmic reticulum stress, and interferon responses

Cited by 373 publications

References 97 publications

X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation to KSHV Reactivation from Latency

X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation to KSHV Reactivation from Latency

Tumor Stress Inside Out: Cell-Extrinsic Effects of the Unfolded Protein Response in Tumor Cells Modulate the Immunological Landscape of the Tumor Microenvironment

Integrated Stress Response Signaling Pathways Induced by Supraphysiological Concentrations of Thyroid Hormone Inhibit Viral Replication

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