Vaccination against Marek's disease reduces telomerase activity and viral gene transcription in peripheral blood leukocytes from challenged chickens

Debba-Pavard, Manel; Aït-Lounis, Aouatef; Soubieux, Denis; Rasschaert, Denis; Dambrine, Ginette

doi:10.1016/j.vaccine.2008.07.038

Cited by 8 publications

(14 citation statements)

References 45 publications

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“…S2 in the supplemental material). Interestingly, as previously described (38), Meq expression was undetectable in the PBL CVI988 D29 library of infection, in contrast to the PBL RB-1B D27 library (see Fig. S2 in the supplemental material).…”

Section: Mirna-21 Is Overexpressed During Natural Infection Withsupporting

confidence: 77%

“…However, we acknowledge that changes in the transactivating properties of CVI988 Meq may not be the only mechanism underlying the lower level of gga-miR-21 expression in CVI988-infected PBLs. The previously described lower level of Meq in PBLs (38), the lower viral replication (58), and other pathways may also be involved in gga-miR-21 regulation in the context of CVI988 infection.…”

Section: Tablementioning

confidence: 81%

“…For the 3 chickens, the level of miR-21 expression increased significantly (P Ͻ 0.05) from 7 dpi onward. At 21 dpi, a time point corresponding to the implementation of lymphomagenesis in our in vivo model (38), the level of miR-21 expression was up two times compared to its level of expression before infection. Expression of viral meq and pp38 genes during infection was assessed by RT-PCR, and amplicons were found, as expected (Fig.…”

Section: Mirna-21 Is Overexpressed During Natural Infection Withmentioning

confidence: 99%

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The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq

Stik

Dambrine

Pfeffer

et al. 2013

J Virol

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cGallid herpesvirus 2 (GaHV-2) is an oncogenic herpesvirus that causes T lymphoma in chicken. GaHV-2 encodes a basic leucine zipper (bZIP) protein of the AP-1 family, Meq. Upon formation of homo-or heterodimers with c-Jun, Meq may modulate the expression of viral and cellular genes involved in lymphomagenesis. GaHV-2 also encodes viral microRNAs (miRNAs) involved in latency and apoptosis escape. However, little is known about cellular miRNA deregulation during the development of GaHV-2-associated lymphoma. We determined the cellular miRNA expression profiles of chickens infected with a very virulent strain (RB-1B) or a vaccine strain (CVI988) or noninfected. Among the most deregulated cellular miRNAs, we focused our efforts on gga-miR-21, which is upregulated during GaHV-2 infection. We mapped the gga-miR-21 promoter to the 10th intron of the TMEM49 gene and found it to be driven by AP-1-and Ets-responsive elements. We show here that the viral oncoprotein Meq binds to this promoter, thereby transactivating gga-miR-21 expression. We confirmed that this miRNA targets chicken programmed death cell 4 (PDCD4) and promotes tumor cell growth and apoptosis escape. Finally, gga-miR-21 was overexpressed only during infection with a very virulent strain (RB-1B) and not during infection with a nononcogenic strain (CVI988), providing further evidence for its role in GaHV-2 lymphomagenesis. Our data therefore suggest an additional role for Meq in GaHV-2-mediated lymphomagenesis through the induction of miR-21 expression.

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Section: Mirna-21 Is Overexpressed During Natural Infection Withsupporting

confidence: 77%

Section: Tablementioning

confidence: 81%

Section: Mirna-21 Is Overexpressed During Natural Infection Withmentioning

confidence: 99%

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The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq

Stik

Dambrine

Pfeffer

et al. 2013

J Virol

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“…In Hu's [39] research, after Tca8113 cells were treated with adriamycin at 5 mg/L for 5 and 7 days, apoptosis was found while telomerase activity dropped in a time-dependent manner. Debba-Pavard [40] investigated whether telomerase activity and viral gene transcription were associated with protection against the RB-1B strain of MDV in chickens vaccinated with Rispens CVI988 or the herpes virus of turkey. Fragnet [41] reported the identification of a virusencoded RNA telomerase subunit (vTR) within the genome of MDV and demonstrated that the vTR promoter region is efficient whatever the species of cell line considered and that vTR is expressed in vivo in peripheral blood leukocytes from chickens infected with oncogenic MDV-RB1B and the vaccine MDV-Rispens strains.…”

Section: Discussionmentioning

confidence: 99%

Telomerase-Mediated Apoptosis of Chicken Lymphoblastoid Tumor Cell Line by Lanthanum Chloride

Zhang

Wang

et al. 2011

Biol Trace Elem Res

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To investigate the biological effects of lanthanum on chicken lymphoid tumors, cultures of the MDCC-MSB1 chicken lymphoblastoid cell line were treated with 2.5 mM lanthanum chloride for 2 days at 12-h intervals. The apoptotic cells were detected using the TdT-mediated dUTP nick end labeling assay and flow cytometer analysis. The telomerase activity and the chTERT mRNA expression levels of the MDCC-MSB1 cells were examined. The results showed that MDCC-MSB1 cell apoptosis occurred after incubation for 12 to 48 h induced by 2.5 mM LaCl(3). Consistent with the apoptosis results, telomerase activities in LaCl(3)-treated cells significantly decreased (P < 0.05) compared with 0 h group. Furthermore, the transcription of chTERT gene in MDCC-MSB1 cell was significantly inhibited in LaCl(3) treatment group (P < 0.05). These results suggest that the decrease of the chTERT transcription and telomerase activity play an important role in the La-induced apoptosis in chicken lymphoid tumor.

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“…Functional analysis has shown that vTR can reconstitute telomerase activity by interacting with chicken TERT (chTERT) more efficiently than chTR [22]. Furthermore, vTR expression increases during GaHV-2 lymphomagenesis and this increase is correlated with the upregulation of telomerase activity, which is not associated with an upregulation of chTERT transcription [23,24]. Telomerase is also activated by a number of human oncogenic viruses [25], but investigations in this case are obviously restricted to in vitro analyses of cell lines derived from tumors or transformed in vitro .…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo

et al. 2010

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BackgroundTelomerase activation, a critical step in cell immortalization and oncogenesis, is partly regulated by alternative splicing. In this study, we aimed to use the Marek's disease virus (MDV) T-cell lymphoma model to evaluate TERT regulation by splicing during lymphomagenesis in vivo, from the start point to tumor establishment.ResultsWe first screened cDNA libraries from the chicken MDV lymphoma-derived MSB-1 T- cell line, which we compared with B (DT40) and hepatocyte (LMH) cell lines. The chTERT splicing pattern was cell line-specific, despite similar high levels of telomerase activity. We identified 27 alternative transcripts of chicken TERT (chTERT). Five were in-frame alternative transcripts without in vitro telomerase activity in the presence of viral or chicken telomerase RNA (vTR or chTR), unlike the full-length transcript. Nineteen of the 22 transcripts with a premature termination codon (PTC) harbored a PTC more than 50 nucleotides upstream from the 3' splice junction, and were therefore predicted targets for nonsense-mediated decay (NMD). The major PTC-containing alternatively spliced form identified in MSB1 (ie10) was targeted to the NMD pathway, as demonstrated by UPF1 silencing. We then studied three splicing events separately, and the balance between in-frame alternative splice variants (d5f and d10f) plus the NMD target i10ec and constitutively spliced chTERT transcripts during lymphomagenesis induced by MDV indicated that basal telomerase activity in normal T cells was associated with a high proportion of in-frame non functional isoforms and a low proportion of constitutively spliced chTERT. Telomerase upregulation depended on an increase in active constitutively spliced chTERT levels and coincided with a switch in alternative splicing from an in-frame variant to NMD-targeted variants.ConclusionsTERT regulation by splicing plays a key role in telomerase upregulation during lymphomagenesis, through the sophisticated control of constitutive and alternative splicing. Using the MDV T-cell lymphoma model, we identified a chTERT splice variant as a new NMD target.

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Vaccination against Marek's disease reduces telomerase activity and viral gene transcription in peripheral blood leukocytes from challenged chickens

Cited by 8 publications

References 45 publications

The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq

The Oncogenic MicroRNA OncomiR-21 Overexpressed during Marek's Disease Lymphomagenesis Is Transactivated by the Viral Oncoprotein Meq

Telomerase-Mediated Apoptosis of Chicken Lymphoblastoid Tumor Cell Line by Lanthanum Chloride

Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo

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