Cloning and Characterization of cDNA Clones Corresponding to Transcripts from the BamHI G Region of the Epstein-Barr Virus Genome and Expression of BGLF2

Chen, Mei‐Ru; Hsu, Tsuey-Ying; Lin, Shi‐Ming; Chen, Jen‐Yang; Yang, Cheng‐Yao

doi:10.1099/0022-1317-72-12-3047

Cited by 15 publications

(9 citation statements)

References 19 publications

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“…BGLF2 is a tegument protein that expressed with late kinetics in EBV-infected cells (33,64,65). Recently, BGLF2 has been shown to activate p38 and JNK signaling pathways and enhance AP-1-dependent transcription (34,35).…”

Section: Discussionmentioning

confidence: 99%

Epstein‐Barr virus tegument protein BGLF2 inhibits NF‐κB activity by preventing p65 Ser536 phosphorylation

et al. 2019

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Epstein‐Barr virus (EBV), a ubiquitous gammaherpesvirus, can regulate the antiviral response of NF‐κB signaling, which is critical for cell survival, growth transformation, and virus latency. Here, we showed that tegument protein BGLF2 could inhibit TNF‐α‐induced NF‐κB activity. BGLF2 was shown to interplay with the NF‐κB subunits p65 and p50, and the Rel homology domain of p65 was the pivotal region to interact with BGLF2. Nonetheless, BGLF2 did not influence the development of p65‐p50 dimerization. Yet, overexpression of BGLF2 inhibited the phosphorylation of p65 Ser536 (but not Ser276) and blocked the nuclear translocation of p65. In addition, knockdown of BGLF2 during EBV lytic replication elevated NF‐κB activity and the phosphorylation of p65 Ser536. Taken together, these results suggest that the inhibition of NF‐κB activation may serve as a strategy to escape the host's antiviral innate immunity to EBV during its lytic infection.—Chen, T., Wang, Y., Xu, Z., Zou, X., Wang, P., Ou, X., Li, Y., Peng, T., Chen, D., Li, M., Cai, M. Epstein‐Barr virus tegument protein BGLF2 inhibits NF‐κB activity by preventing p65 Ser536 phosphorylation. FASEB J. 33, 10563–10576 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Epstein‐Barr virus tegument protein BGLF2 inhibits NF‐κB activity by preventing p65 Ser536 phosphorylation

et al. 2019

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“…BGLF2 is a tegument protein (41) that is expressed with late kinetics and localizes to the nuclei of virus-infected cells undergoing lytic infection (42). BGLF2 interacts with NIMA-related protein kinase (NEK9) and GEM-interacting protein (GMIP), induces expression of p21, and induces cell cycle arrest at the G 1 /S transition (43).…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

Liu

Cohen

2016

J Virol

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IMPORTANCE Epstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency. E pstein-Barr virus (EBV) is a cause of infectious mononucleosis and is associated with both B lymphocyte and epithelial cell malignancies. EBV encodes a number of proteins that trigger cell signaling pathways, such as AP-1, JAK-STAT, NF-B, and phosphatidylinositol 3-kinase (PI3K)/Akt, which are critical for cell survival, virus latency, and growth transformation (1-6). For example, EBV latent membrane protein 1 (LMP1) mimics CD40 signaling and is important for EBV-induced B cell growth proliferation, inhibition of apoptosis, and EBV transformation. LMP1 interacts with tumor necrosis factor receptor-associated factors (TRAFs), leading to activation of NF-B, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), PI3K/Akt, and STAT3 (7-12). EBV LMP2A mimics B cell receptor signaling and contributes to the long-term survival of B cells (13-16). LMP2A activates extracellular signal-related protein kinase (ERK), PI3K/Akt, and JNK (17) and downregulates NF-B and STAT signaling pathways (18). The EBV immediate early protein BZLF1 activates virus reactivation from latency (19-21). BZLF1 activates p38 and JNK to turn on the ATF2 transcription factor (22). BRLF1, another EBV immediate early protein, activates the AP-1 pathway by increasing the levels of phosphorylated p38, JNK, and ERK (22, 23) and induces phosphorylation of Akt through the PI3K pathway (24). Activation of Akt, ERK, and p38 signaling is required for EBV reactivation from latency (25-28).To identify additional EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 promoter activity in AP-1-luciferase reporter assays. We found that the EBV tegument protein BGLF2 induced AP-1 reporter activity and activated p38 and JNK. BGLF2 promoted EBV reactivation by enhancing BZLF1 expression and EBV production, and p38 activation by BGLF2 was required for these activities. Citation Liu X, Cohen JI. 2016. Epstein-Barr virus (EBV) tegument protein BGLF2 promotes EBV reactivation through activation of the p38 mitogen-activated protein kinase.

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“…Instead of testing each of the other seven candidates individually, the 40-kDa protein was analyzed directly by MS and shown to be the product of the HSV-1 U L 16 gene. The herpesvirus U L 16 gene family encodes a group of small (33-to 40-kDa), conserved proteins that are produced late in the viral life cycle and packaged into virions (9,29,31,43). Members of this protein family, which includes HSV-1 UL16, cytomegalovirus UL94, Epstein-Barr virus BGLF2, and varicella-zoster virus ORF44, contain potential Zn finger domains in the conserved C terminus and a potential nuclear localization signal in the N terminus (43).…”

Section: Discussionmentioning

confidence: 99%

Binding Partners for the UL11 Tegument Protein of Herpes Simplex Virus Type 1

Loomis

Courtney

Wills

2003

J Virol

102

186

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The product of the U L 11 gene of herpes simplex virus type 1 (HSV-1) is a 96-amino-acid tegument protein that accumulates on the cytoplasmic face of internal membranes. Although it is thought to be important for nucleocapsid envelopment and egress, the actual function of this protein is unknown. Previous studies focused on the characterization of sequence elements within the UL11 protein that function in membrane binding and trafficking to the Golgi apparatus. Binding was found to be mediated by two fatty acyl groups (myristate and palmitate), while an acidic cluster and a dileucine motif were identified as being important for the recycling of UL11 from the plasma membrane to the Golgi apparatus. The goal of the experiments described here was to identify and characterize binding partners (viral or cellular) of UL11. Using both immunoprecipitation and glutathione S-transferase (GST) pull-down assays, we identified a 40-kDa protein that specifically associates with UL11 from infected Vero cells. Mutational analyses revealed that the acidic cluster and the dileucine motif are required for this association, whereas the entire second half of UL11 is not. In addition, UL11 homologs from pseudorabies and Marek's disease herpesviruses were also found to be capable of binding to the 40-kDa protein from HSV-1-infected cells, suggesting that the interaction is conserved among alphaherpesviruses. Purification and analysis of the 40-kDa protein by mass spectrometry revealed that it is the product of the U L 16 gene, a virion protein reported to be involved in nucleocapsid assembly. Cells transfected with a UL16-green fluorescent protein expression vector produced a protein that was of the expected size, could be pulled down with GST-UL11, and accumulated in a Golgi-like compartment only when coexpressed with UL11, indicating that the interaction does not require any other viral products. These data represent the first steps toward elucidating the network of tegument proteins that UL11 links to membranes.During herpes simplex virus type 1 (HSV-1) assembly, over 30 different proteins come together to form three major structures: the nucleocapsid, the glycoprotein-containing envelope, and the collection of proteins located between the capsid and the envelope, known as the tegument (33). As with other herpesviruses, the most recent model for HSV-1 envelopment suggests that assembled nucleocapsids are shuttled out of the nucleus by budding and fusion events on the inner and outer nuclear membranes, respectively, and then travel through the cytoplasm until reaching trans-Golgi network (TGN)-derived vesicles (reviewed in reference 27). At this site, nucleocapsids are thought to acquire their final lipid bilayer in a process that also results in the acquisition of the tegument and glycoproteins. The mature virions subsequently follow the secretory pathway out to the cell surface, where they are released into the extracellular medium. Although several lines of evidence support this model, the specific molecular mechanisms by which t...

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Cloning and Characterization of cDNA Clones Corresponding to Transcripts from the BamHI G Region of the Epstein-Barr Virus Genome and Expression of BGLF2

Cited by 15 publications

References 19 publications

Epstein‐Barr virus tegument protein BGLF2 inhibits NF‐κB activity by preventing p65 Ser536 phosphorylation

Epstein‐Barr virus tegument protein BGLF2 inhibits NF‐κB activity by preventing p65 Ser536 phosphorylation

Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

Binding Partners for the UL11 Tegument Protein of Herpes Simplex Virus Type 1

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