Cell Membrane-bound Kaposi's Sarcoma-associated Herpesvirus-encoded Glycoprotein B Promotes Virus Latency by Regulating Expression of Cellular Egr-1

Dyson, Ossie F.; Traylen, Christopher; Akula, Shaw M.

doi:10.1074/jbc.m110.159103

Cited by 27 publications

(52 citation statements)

References 71 publications

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“…However, enhanced cellular Egr-1 and viral RTA expression during early stages of primary infection (Fig. 3) is not sufficient to trigger a lytic infection [6]. These results suggest the following: (i) the role of Egr-1.RTA signaling in initiating a lytic cycle of infection during the course of initial infection of cells is limited; and (ii) there is a missing element in the Egr-1.RTA driven cellular events critical for inducing a productive replication.…”

Section: Discussionmentioning

confidence: 97%

Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1

et al. 2012

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In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1–3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50 , the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter ( ORF50 P) in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.

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Section: Discussionmentioning

confidence: 97%

Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1

et al. 2012

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“…Therefore, the shear rate of the shear product DRz dissociation process is relatively small [45, 46]. The RNA of the DNA-RNA hybrid molecules can be degraded by the RNA enzyme H. Hence, the DNA enzyme can not only directly kill the target RNA such as Rz, but also cause the hydrolysis of the RNA enzyme H to target RNAs, such as ASODN [47, 48]. …”

Section: Discussionmentioning

confidence: 99%

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Wang

Cheng

et al. 2013

BioMed Research International

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The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz) as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft.

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“…Envelope glycoprotein gB interacts with a variety of cell surface molecules including heparan sulfate and integrins to facilitate virus binding and entry [9, 17]. There is growing evidence that demonstrates significant roles of gB interactions to modulate a variety of cell signaling pathways to induce a cellular state that is receptive for virus replication [13, 14, 23, 37]. In a recent study, we demonstrated cell membrane-associated gB to promote adhesion over migration of infected cells via RGD motif [13].…”

Section: Discussionmentioning

confidence: 99%

Membrane-Associated Kaposi Sarcoma-Associated Herpesvirus Glycoprotein B Promotes Cell Adhesion and Inhibits Migration of Cells via Upregulating IL-1β and TNF-α

2017

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Objectives: Kaposi sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is expressed on the viral envelope as well as on the cytoplasmic membrane of infected cells. In the current study, we aimed to decipher the impact of membrane-associated gB on adhesion and migration of cells via modulating the expression of cytokines. Methods: A combination of polymerase chain reaction array, cell adhesion assay, and wound-healing migration assay was conducted to study the influence of the gB-induced cytokines on cell adhesion and migration. Results: Membrane-associated gB was demonstrated to significantly upregulate the expression of IL-1β and TNF-α. Elevated levels of these cytokines were observed in conditioned medium (CM) collected from gB-expressing cells (gB-CM) compared to CM collected from untransfected cells or cells transfected with empty vector. KSHV gB-induced IL-1β and TNF-α play a role in the ability of gB-CM to mediate cell adhesion while inhibiting migration. Conclusion: Our results provide novel evidence that demonstrates full-length gB expressed on cell membrane to mediate adhesion and inhibit migration of cells not only by autocrine mechanism mediated by RGD-based interactions [Hussein et al.: BMC Cancer 2016; 16: 148], but also by paracrine mechanism mediated by gB-induced IL-1β and TNF-α.

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Cell Membrane-bound Kaposi's Sarcoma-associated Herpesvirus-encoded Glycoprotein B Promotes Virus Latency by Regulating Expression of Cellular Egr-1

Cited by 27 publications

References 71 publications

Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1

Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1

Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

Membrane-Associated Kaposi Sarcoma-Associated Herpesvirus Glycoprotein B Promotes Cell Adhesion and Inhibits Migration of Cells via Upregulating IL-1β and TNF-α

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