scholarly journals Inhibition of Marek's disease virus replication by retroviral vector-based RNA interference

Virology ◽  
2008 ◽  
Vol 377 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Mo Chen ◽  
William S. Payne ◽  
Henry Hunt ◽  
Huanmin Zhang ◽  
Sheri L. Holmen ◽  
...  
Keyword(s):  
Rna Interference ◽  
Disease Virus ◽  
Virus Replication ◽  
Retroviral Vector ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

Relationship between tumour development and detection of Marek’s disease virus in the feather follicular epithelium of older chickens

2012 ◽  
Vol 60 (3) ◽  
pp. 333-342
Author(s):  
Mitsutaka Ikezawa ◽  
Jun Sasaki ◽  
Masanobu Goryo
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Marek's Disease Virus ◽  
Lymphoid Cells ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Tumour Development ◽  
Group A ◽  
The Relationship

To demonstrate the relationship between tumour development and virus replication, eight specific-pathogen-free pullets of line P2 (Group P; 14 weeks old) and five adult chickens (Group A; 96 weeks old) were inoculated with virulent Marek’s disease virus (vMDV). Five chickens of Group P died or were euthanised due to moribund condition following the development of neoplastic lesions between days 53 and 91. On histopathological examination, these lesions were characterised by the proliferation of lymphoid cells of variable size. On analysis by polymerase chain reaction (PCR), the MDVmeqgene was detected in Group P from day 21, and it was continuously identified in five chickens until they died or were euthanised. Abnormal signs and histopathological changes were not observed in chickens of Group A. The MDVmeqgene was temporarily detected in some chickens of Group A, but it remained almost undetectable throughout the experimental period. In older chickens inoculated with vMDV, the onset of MD lymphoma development tended to be delayed as compared with the young chicks. The relationship between MD lymphoma development and virus replication in older chickens has been suggested. Our data might indicate the underlying existence of an age-related resistance to vMDV challenge.

scholarly journals Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Xue Lian ◽  
Chenyi Bao ◽  
Xueqi Li ◽  
Xunhai Zhang ◽  
Hongjun Chen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Viral Replication ◽  
Disease Virus ◽  
Virus Replication ◽  
Specific Inhibitor ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Stat3 Phosphorylation

ABSTRACT Oncogenic virus replication often leads to genomic instability, causing DNA damage and inducing the DNA damage response (DDR) pathway. The DDR pathway is a cellular pathway that senses DNA damage and regulates the cell cycle to maintain genomic stability. Therefore, the DDR pathway is critical for the viral lifecycle and tumorigenesis. Marek’s disease virus (MDV), an alphaherpesvirus that causes lymphoma in chickens, has been shown to induce DNA damage in infected cells. However, the interaction between MDV and the host DDR is unclear. In this study, we observed that MDV infection causes DNA strand breakage in chicken fibroblast (CEF) cells along with an increase in the DNA damage markers p53 and p21. Interestingly, we showed that phosphorylation of STAT3 was increased during MDV infection, concomitantly with a decrease of Chk1 phosphorylation. In addition, we found that MDV infection was enhanced by VE-821, an ATR-specific inhibitor, but attenuated by hydroxyurea, an ATR activator. Moreover, inhibition of STAT3 phosphorylation by Stattic eliminates the ability of MDV to inhibit Chk1 phosphorylation. Finally, we showed that MDV replication was decreased by Stattic treatment. Taken together, these results suggest that MDV disables the ATR-Chk1 pathway through STAT3 activation to benefit its replication. IMPORTANCE MDV is used as a biomedical model to study virus-induced lymphoma due to the similar genomic structures and physiological characteristics of MDV and human herpesviruses. Upon infection, MDV induces DNA damage, which may activate the DDR pathway. The DDR pathway has a dual impact on viruses because it manipulates repair and recombination factors to facilitate viral replication and also initiates antiviral action by regulating other signaling pathways. Many DNA viruses evolve to manipulate the DDR pathway to promote virus replication. In this study, we identified a mechanism used by MDV to inhibit ATR-Chk1 pathways. ATR is a cellular kinase that responds to broken single-stranded DNA, which has been less studied in MDV infection. Our results suggest that MDV infection activates STAT3 to disable the ATR-Chk1 pathway, which is conducive to viral replication. This finding provides new insight into the role of STAT3 in interrupting the ATR-Chk1 pathway during MDV replication.

Targeting Marek's disease virus by RNA interference delivered from a herpesvirus vaccine

Vaccine ◽  
2009 ◽  
Vol 27 (2) ◽  
pp. 298-306 ◽  
Author(s):  
Luke S. Lambeth ◽  
Yuguang Zhao ◽  
Lorraine P. Smith ◽  
Lydia Kgosana ◽  
Venugopal Nair
Keyword(s):  
Rna Interference ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

Effect of Phosphonoacetate on Marek's Disease Virus Replication

1976 ◽  
Vol 56 (4) ◽  
pp. 823-827 ◽  
Author(s):  
Lucy F. Lee ◽  
K. Nazerian ◽  
Susan S. Leinbach ◽  
J. M. Reno ◽  
J. A. Boezi
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

scholarly journals Marek's disease virus requires both copies of the inverted repeat regions for efficient in vivo replication and pathogenesis

2020 ◽  
Author(s):  
Tereza Vychodil ◽  
Andelé M. Conradie ◽  
Jakob Trimpert ◽  
Amr Aswad ◽  
Luca D. Bertzbach ◽  
...  
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Repeat Region ◽  
Internal Repeat

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus of chickens. The MDV genome consists of two unique regions that are both flanked by inverted repeat regions. These repeats harbor several genes involved in virus replication and pathogenesis, but it remains unclear why MDV and other herpesviruses harbor these large sequence duplications. In this study, we set to determine if both copies of these repeat regions are required for MDV replication and pathogenesis. Our results demonstrate that MDV mutants lacking the entire internal repeat region (ΔIRLS) efficiently replicate and spread from cell-to-cell in vitro. However, ΔIRLS replication was severely impaired in infected chickens and the virus caused significantly less frequent disease and tumors compared to the controls. In addition, we also generated recombinant viruses that harbor a deletion of most of the internal repeat region, leaving only short terminal sequences behind (ΔIRLS-HR). These remaining homologous sequences facilitated rapid restoration of the deleted repeat region, resulting in a virus that caused disease and tumors comparable to the wild type. Therefore, ΔIRLS-HR represents an excellent platform for rapid genetic manipulation of the virus genome in the repeat regions. Taken together, our study demonstrates that MDV requires both copies of the repeats for efficient replication and pathogenesis in its natural host. IMPORTANCE Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes losses in the poultry industry of up to $2 billion per year. The virus is also widely used as a model to study alphaherpesvirus pathogenesis and virus-induced tumor development in a natural host. MDV and most other herpesviruses harbor direct or inverted repeats regions in their genome. However, the role of these sequence duplications in MDV remains elusive and has never been investigated in a natural virus-host model for any herpesvirus. Here, we demonstrate that both copies of the repeats are needed for efficient MDV replication and pathogenesis in vivo, while replication was not affected in cell culture. With this, we further dissect herpesvirus genome biology and the role of repeat regions in Marek's disease virus replication and pathogenesis.

scholarly journals Marek's Disease Virus-Encoded vIL-8 Gene Is Involved in Early Cytolytic Infection but Dispensable for Establishment of Latency

2004 ◽  
Vol 78 (9) ◽  
pp. 4753-4760 ◽  
Author(s):  
Xiaoping Cui ◽  
Lucy F. Lee ◽  
Willie M. Reed ◽  
Hsing-Jien Kung ◽  
Sanjay M. Reddy
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Virus Titer ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Wild Type Virus ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Wild Type

ABSTRACT Marek's disease, a lymphoproliferative disease of chickens, is caused by an alphaherpesvirus, Marek's disease virus (MDV). This virus encodes a virokine, vIL-8, with general homology to cellular CXC chemokines such as interleukin-8 (IL-8) and Gro-α. To study the function of vIL-8 gene, we deleted both copies of vIL-8 residing in the terminal repeat long and internal repeat long region of the viral genome and generated a mutant virus with vIL-8 deleted, rMd5/ΔvIL-8. Growth kinetics study showed that vIL-8 gene is dispensable for virus replication in cell culture. In vivo, the vIL-8 gene is involved in early cytolytic infections in lymphoid organs, as evidenced by limited viral antigen expression of rMd5/ΔvIL-8. However, the rMd5/ΔvIL-8 virus is unimpaired in virus replication in the feather follicle epithelium. vIL-8 does not appear to be important for establishment of latency, since rMd5/ΔvIL-8 and the wild-type virus have similar viremia titers at 14 days postinfection, a period when the virus titer comes primarily from reactivated latent genomes. Nevertheless, because of the impaired cytolytic infections, the overall transformation efficiency of the virus with vIL-8 deleted is much lower, as reflected by the reduced number of transformed cells at 5 weeks postinoculation and the presence of fewer gross tumors. Importantly, the revertant virus that restored the expression of vIL-8 gene also restored the wild-type phenotype, indicating the deficient phenotypes are results of vIL-8 deletion. One of the interesting differences between the MDV vIL-8 gene and its cellular counterpart is the presence of a DKR (Asp-Lys-Arg) motif instead of ELR (Glu-Leu-Arg) preceding the invariable CXC motif. To study the significance of this variation, we generated recombinant MDV, rMd5/vIL-8-ELR, carrying the ELR motif. Both in vitro and in vivo studies revealed that the DKR motif is as competent as ELR in pathogenesis of MDV.

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