Assembly of Epstein-Barr Virus Capsid in Promyelocytic Leukemia Nuclear Bodies

Wang, Wen Hung; Kuo, Chung-Wen; Chang, Li-Kwan; Hung, Chen-Chia; Tzu-Hsuan, Chang; Liu, Shih‐Tung

doi:10.1128/jvi.01114-15

Cited by 18 publications

(16 citation statements)

References 62 publications

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“…Viral CPs are the building blocks of the viral capsid, but in addition to this structural role they can play a number of others throughout the viral infection. Examples in animal viruses exist demonstrating that CPs can re-localize within the cell in the presence of other viral proteins or during the viral infection ( Wistuba et al, 1997 ; Shishido-Hara et al, 2000 ; Wang et al, 2015 ). In the case of the geminivirus TYLCV, subcellular localization of the CP has been previously studied ( Rojas et al, 2001 ); however, in these experiments the CP was expressed in isolation, and therefore in the absence of other viral proteins, the viral genome, and the cellular changes triggered by the viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…In the dsDNA human polyomavirus JC, one of the CPs, named VP1, is efficiently transported to the nucleus and localized in discrete nuclear speckles only in the presence of the other two CPs, VP2 and VP3 ( Shishido-Hara et al, 2000 ). A similar case is that of Epstein-Barr virus, in which one of four CPs, BORF1, modifies the subcellular localization of the other three ( Wang et al, 2015 ). These drastic virus-regulated changes in the subcellular distribution of CPs could at least partially underlie multifunctionality of this protein in a timely manner along the infection of a given cell.…”

Section: Introductionmentioning

confidence: 91%

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Dynamic Virus-Dependent Subnuclear Localization of the Capsid Protein from a Geminivirus

Wang

Tan

et al. 2017

Front. Plant Sci.

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Viruses are intracellular parasites with a nucleic acid genome and a proteinaceous capsid. Viral capsids are formed of at least one virus-encoded capsid protein (CP), which is often multifunctional, playing additional non-structural roles during the infection cycle. In animal viruses, there are examples of differential localization of CPs associated to the progression of the infection and/or enabled by other viral proteins; these changes in the distribution of CPs may ultimately regulate the involvement of these proteins in different viral functions. In this work, we analyze the subcellular localization of a GFP- or RFP-fused CP from the plant virus Tomato yellow leaf curl virus (TYLCV; Fam. Geminiviridae) in the presence or absence of the virus upon transient expression in the host plants Nicotiana benthamiana and tomato. Our findings show that, in agreement with previous reports, when the CP is expressed alone it localizes mainly in the nucleolus and weakly in the nucleoplasm. Interestingly, the presence of the virus causes the sequential re-localization of the CP outside of the nucleolus and into discrete nuclear foci and, eventually, into an uneven distribution in the nucleoplasm. Expression of the viral replication-associated protein, Rep, is sufficient to exclude the CP from the nucleolus, but the localization of the CP in the characteristic patterns induced by the virus cannot be recapitulated by co-expression with any individual viral protein. Our results demonstrate that the subcellular distribution of the CP is a dynamic process, temporally regulated throughout the progression of the infection. The regulation of the localization of the CP is determined by the presence of other viral components or changes in the cellular environment induced by the virus, and is likely to contribute to the multifunctionality of this protein. Bearing in mind these observations, we suggest that viral proteins should be studied in the context of the infection and considering the temporal dimension in order to comprehensively understand their roles and effects in the interaction between virus and host.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Dynamic Virus-Dependent Subnuclear Localization of the Capsid Protein from a Geminivirus

Wang

Tan

et al. 2017

Front. Plant Sci.

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“…Overexpression of Zta in EBV latently infected cells results in dispersion of PML nuclear bodies and induces loss of SUMO1-modified isoforms of PML protein [59, 60]. Knockdown of PML reduces the production of viral particles and EBV genome in EBV-positive P3HR1 cells, supporting the concept that PML nuclear bodies play a role in EBV capsid assembly and viral lytic DNA replication [61]. …”

Section: Introductionmentioning

confidence: 97%

Arsenic trioxide inhibits EBV reactivation and promotes cell death in EBV-positive lymphoma cells

Yin

Sides

Parsons³

et al. 2017

Virol J

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BackgroundEpstein-Barr Virus (EBV) is associated with hematopoietic malignancies, such as Burkitt’s lymphoma, post-transplantation lymphoproliferative disorder, and diffuse large B-cell lymphoma. The current approach for EBV-associated lymphoma involves chemotherapy to eradicate cancer cells, however, normal cells may be injured and organ dysfunction may occur with currently employed regimens. This research is focused on employing arsenic trioxide (ATO) as EBV-specific cancer therapy takes advantage of the fact the EBV resides within the malignant cells.Methods and resultsOur research reveals that low ATO inhibits EBV gene expression and genome replication. EBV spontaneous reactivation starts as early as 6 h after re-suspending EBV-positive Mutu cells in RPMI media in the absence of ATO, however this does not occur in Mutu cells cultured with ATO. ATO’s inhibition of EBV spontaneous reactivation is dose dependent. The expression of the EBV immediate early gene Zta and early gene BMRF1 is blocked with low concentrations of ATO (0.5 nM – 2 nM) in EBV latency type I cells and EBV-infected PBMC cells. The combination of ATO and ganciclovir further diminishes EBV gene expression. ATO-mediated reduction of EBV gene expression can be rescued by co-treatment with the proteasome inhibitor MG132, indicating that ATO promotes ubiquitin conjugation and proteasomal degradation of EBV genes. Co-immunoprecipitation assays with antibodies against Zta pulls down more ubiquitin in ATO treated cell lysates. Furthermore, MG132 reverses the inhibitory effect of ATO on anti-IgM-, PMA- and TGF-β-mediated EBV reactivation. Thus, mechanistically ATO’s inhibition of EBV gene expression occurs via the ubiquitin pathway. Moreover, ATO treatment results in increased cell death in EBV-positive cells compared to EBV-negative cells, as demonstrated by both MTT and trypan blue assays. ATO-induced cell death in EBV-positive cells is dose dependent. ATO and ganciclovir in combination further enhances cell death specifically in EBV-positive cells.ConclusionATO-mediated inhibition of EBV lytic gene expression results in cell death selectively in EBV-positive lymphocytes, suggesting that ATO may potentially serve as a drug to treat EBV-related lymphomas in the clinical setting.

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“…Most efforts have focused on understanding capsid assembly (32, 33), which occurs at promyelocytic leukemia nuclear bodies (34), and initial nuclear egress. Nuclear egress requires the dimeric complex of BFRF1 and BFLF2 (27, 35, 36), homologs of the nuclear egress complex proteins of alpha and betaherpesviruses, which are critical for budding into the perinuclear space, and the viral kinase BGLF4 (37).…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus glycoprotein gM can interact with the cellular protein p32 and knockdown of p32 impairs virus

et al. 2016

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The Epstein-Barr virus glycoprotein complex gMgN has been implicated in assembly and release of fully enveloped virus, although the precise role that it plays has not been elucidated. We report here that the long predicted cytoplasmic tail of gM is not required for complex formation and that it interacts with the cellular protein p32, which has been reported to be involved in nuclear egress of human cytomegalovirus and herpes simplex virus. Although redistribution of p32 and colocalization with gM was not observed in virus infected cells, knockdown of p32 expression by siRNA or lentivirus-delivered shRNA recapitulated the phenotype of a virus lacking expression of gNgM. A proportion of virus released from cells sedimented with characteristics of virus lacking an intact envelope and there was an increase in virus trapped in nuclear condensed chromatin. The observations suggest the possibility that p32 may also be involved in nuclear egress of Epstein-Barr virus.

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Assembly of Epstein-Barr Virus Capsid in Promyelocytic Leukemia Nuclear Bodies

Cited by 18 publications

References 62 publications

Dynamic Virus-Dependent Subnuclear Localization of the Capsid Protein from a Geminivirus

Dynamic Virus-Dependent Subnuclear Localization of the Capsid Protein from a Geminivirus

Arsenic trioxide inhibits EBV reactivation and promotes cell death in EBV-positive lymphoma cells

Epstein–Barr virus glycoprotein gM can interact with the cellular protein p32 and knockdown of p32 impairs virus

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