Interferon Modulation of Marek's Disease Virus Genome Expression in Chicken Cell Lines

1996 ◽  
Vol 40 (1) ◽  
pp. 78 ◽  
Author(s):  
Lucia M. Volpini ◽  
Bruce W. Calnek ◽  
Barbara Sneath ◽  
Margaret J. Sekellick ◽  
Philip I. Marcus
Keyword(s):  
Disease Virus ◽  
Cell Lines ◽  
Virus Genome ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Genome Expression ◽  
Chicken Cell

scholarly journals Marek's Disease Virus-Encoded MicroRNA 155 Ortholog Critical for the Induction of Lymphomas Is Not Essential for the Proliferation of Transformed Cell Lines

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Yaoyao Zhang ◽  
Na Tang ◽  
Jun Luo ◽  
Man Teng ◽  
Katy Moffat ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Virus ◽  
Cell Lines ◽  
Critical Role ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
T Cell Lymphomas

ABSTRACT MicroRNAs (miRNAs) are small noncoding RNAs with profound regulatory roles in many areas of biology, including cancer. MicroRNA 155 (miR-155), one of the extensively studied multifunctional miRNAs, is important in several human malignancies such as diffuse large B cell lymphoma and chronic lymphocytic leukemia. Moreover, miR-155 orthologs KSHV-miR-K12-11 and MDV-miR-M4, encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) and Marek’s disease virus (MDV), respectively, are also involved in oncogenesis. In MDV-induced T-cell lymphomas and in lymphoblastoid cell lines derived from them, MDV-miR-M4 is highly expressed. Using excellent disease models of infection in natural avian hosts, we showed previously that MDV-miR-M4 is critical for the induction of T-cell lymphomas as mutant viruses with precise deletions were significantly compromised in their oncogenicity. However, those studies did not elucidate whether continued expression of MDV-miR-M4 is essential for maintaining the transformed phenotype of tumor cells. Here using an in situ CRISPR/Cas9 editing approach, we deleted MDV-miR-M4 from the MDV-induced lymphoma-derived lymphoblastoid cell line MDCC-HP8. Precise deletion of MDV-miR-M4 was confirmed by PCR, sequencing, quantitative reverse transcription-PCR (qRT-PCR), and functional analysis. Continued proliferation of the MDV-miR-M4-deleted cell lines demonstrated that MDV-miR-M4 expression is not essential for maintaining the transformed phenotype, despite its initial critical role in the induction of lymphomas. Ability to examine the direct role of oncogenic miRNAs in situ in tumor cell lines is valuable in delineating distinct determinants and pathways associated with the induction or maintenance of transformation in cancer cells and will also contribute significantly to gaining further insights into the biology of oncogenic herpesviruses. IMPORTANCE Marek’s disease virus (MDV) is an alphaherpesvirus associated with Marek’s disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype.

Mapping of Marek's disease virus genome: Identification of junction sequences between unique and inverted repeat regions

Virus Genes ◽  
1994 ◽  
Vol 8 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Koichi Makimura ◽  
Fang-Yu Peng ◽  
Miho Tsuji ◽  
Saori Hasegawa ◽  
Yuri Kawai ◽  
...  
Keyword(s):  
Disease Virus ◽  
Inverted Repeat ◽  
Virus Genome ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

scholarly journals Targeted Editing of the pp38 Gene in Marek’s Disease Virus-Transformed Cell Lines Using CRISPR/Cas9 System

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 391 ◽  
Author(s):  
Yaoyao Zhang ◽  
Jun Luo ◽  
Na Tang ◽  
Man Teng ◽  
Vishwanatha R.A.P. Reddy ◽  
...  
Keyword(s):  
Disease Virus ◽  
Cell Lines ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Viral Gene ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Transformed Cell ◽  
Transformed Cell Lines

Marek’s disease virus (MDV), a lymphotropic α-herpesvirus associated with T-cell lymphomas in chickens, is an excellent model for herpesvirus biology and virus-induced oncogenesis. Marek’s disease (MD) is also one of the cancers against which a vaccine was first used. In the lymphomas and lymphoblastoid cell lines (LCLs) derived from them, MDV establishes latent infection with limited gene expression. Although LCLs are valuable for interrogating viral and host gene functions, molecular determinants associated with the maintenance of MDV latency and lytic switch remain largely unknown, mainly due to the lack of tools for in situ manipulation of the genomes in these cell lines. Here we describe the first application of CRISPR/Cas9 editing approach for precise editing of the viral gene phosphoprotein 38 (pp38), a biomarker for latent/lytic switch in MDV-transformed LCLs MDCC-MSB-1 (Marek’s disease cell line MSB-1) and MDCC-HP8. Contradictory to the previous reports suggesting that pp38 is involved in the maintenance of transformation of LCL MSB-1 cells, we show that pp38-deleted cells proliferated at a significant higher rate, suggesting that pp38 is dispensable for the transformed state of these cell lines. Application of CRISPR/Cas9-based gene editing of MDV-transformed cell lines in situ opens up further opportunities towards a better understanding of MDV pathogenesis and virus-host interactions.

scholarly journals Self-excision of the BAC sequences from the recombinant Marek's disease virus genome increases replication and pathogenicity

2008 ◽  
Vol 5 (1) ◽  
pp. 19 ◽  
Author(s):  
Yuguang Zhao ◽  
Lawrence Petherbridge ◽  
Lorraine P Smith ◽  
Sue Baigent ◽  
Venugopal Nair
Keyword(s):  
Disease Virus ◽  
Virus Genome ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease
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