scholarly journals Manipulation of Promyelocytic Leukemia Protein Nuclear Bodies by Marek’s Disease Virus Encoded US3 Protein Kinase

2021 ◽  
Vol 9 (4) ◽  
pp. 685
Author(s):  
Yifei Liao ◽  
Blanca Lupiani ◽  
Sanjay M. Reddy
Keyword(s):  
Protein Kinase ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Marek's Disease ◽  
Dependent Manner ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Promyelocytic Leukemia Protein

Promyelocytic leukemia protein nuclear bodies (PML-NBs) are dynamic nuclear structures, shown to be important for herpesvirus replication; however, their role in regulating Marek’s disease virus (MDV) infection has not been studied. MDV is an oncogenic alphaherpesvirus that causes lymphoproliferative disease in chickens. MDV encodes a US3 serine/threonine protein kinase that is important for MDV replication and gene expression. In this study, we studied the role of MDV US3 in regulating PML-NBs. Using an immunofluorescence assay, we found that MDV US3 disrupts PML and SP100 in a kinase dependent manner. In addition, treatment with MG-132 (a proteasome inhibitor) could partially restore the levels of PML and SP100, suggesting that a cellular proteasome dependent degradation pathway is involved in MDV US3 induced disruption of PML and SP100. These findings provide the first evidence for the interplay between MDV proteins and PML-NBs.

scholarly journals Marek’s disease virus US3 protein kinase phosphorylates chicken HDAC 1 and 2 and regulates viral replication and pathogenesis

2021 ◽  
Vol 17 (2) ◽  
pp. e1009307
Author(s):  
Yifei Liao ◽  
Blanca Lupiani ◽  
Mohammad AI-Mahmood ◽  
Sanjay M. Reddy
Keyword(s):  
Protein Kinase ◽  
Disease Virus ◽  
Specific Inhibitor ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Virus Growth ◽  
Histone Deacetylase 1

Marek’s disease virus (MDV) is a potent oncogenic alphaherpesvirus that elicits a rapid onset of malignant T-cell lymphomas in chickens. Three MDV types, including GaHV-2 (MDV-1), GaHV-3 (MDV-2) and MeHV-1 (HVT), have been identified and all encode a US3 protein kinase. MDV-1 US3 is important for efficient virus growth in vitro. To study the role of US3 in MDV replication and pathogenicity, we generated MDV-1 US3-null virus and chimeric viruses by replacing MDV-1 US3 with MDV-2 or HVT US3. Using MD as a natural virus-host model, we showed that both MDV-2 and HVT US3 partially rescued the growth deficiency of MDV-1 US3-null virus. In addition, deletion of MDV-1 US3 attenuated the virus resulting in higher survival rate and lower MDV specific tumor incidence, which could be partially compensated by MDV-2 and HVT US3. We also identified chicken histone deacetylase 1 (chHDAC1) as a common US3 substrate for all three MDV types while only US3 of MDV-1 and MDV-2 phosphorylate chHDAC2. We further determined that US3 of MDV-1 and HVT phosphorylate chHDAC1 at serine 406 (S406), while MDV-2 US3 phosphorylates S406, S410, and S415. In addition, MDV-1 US3 phosphorylates chHDAC2 at S407, while MDV-2 US3 targets S407 and S411. Furthermore, biochemical studies show that MDV US3 mediated phosphorylation of chHDAC1 and 2 affect their stability, transcriptional regulation activity, and interaction network. Using a class I HDACs specific inhibitor, we showed that MDV US3 mediated phosphorylation of chHDAC1 and 2 is involved in regulation of virus replication. Overall, we identified novel substrates for MDV US3 and characterized the role of MDV US3 in MDV pathogenesis.

scholarly journals Horizontal Transmission of Marek's Disease Virus Requires US2, the UL13 Protein Kinase, and gC

2007 ◽  
Vol 81 (19) ◽  
pp. 10575-10587 ◽  
Author(s):  
Keith W. Jarosinski ◽  
Neil G. Margulis ◽  
Jeremy P. Kamil ◽  
Stephen J. Spatz ◽  
Venugopal K. Nair ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Disease Virus ◽  
Horizontal Transmission ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Artificial Chromosomes ◽  
Multiple Organs

ABSTRACT Marek's disease virus (MDV) causes a general malaise in chickens that is mostly characterized by the development of lymphoblastoid tumors in multiple organs. The use of bacterial artificial chromosomes (BACs) for cloning and manipulation of the MDV genome has facilitated characterization of specific genes and genomic regions. The development of most MDV BACs, including pRB-1B-5, derived from a very virulent MDV strain, involved replacement of the US2 gene with mini-F vector sequences. However, when reconstituted viruses based on pRB-1B were used in pathogenicity studies, it was discovered that contact chickens housed together with experimentally infected chickens did not contract Marek's disease (MD), indicating a lack of horizontal transmission. Staining of feather follicle epithelial cells in the skins of infected chickens showed that virus was present but was unable to be released and/or infect susceptible chickens. Restoration of US2 and removal of mini-F sequences within viral RB-1B did not alter this characteristic, although in vivo viremia levels were increased significantly. Sequence analyses of pRB-1B revealed that the UL13, UL44, and US6 genes encoding the UL13 serine/threonine protein kinase, glycoprotein C (gC), and gD, respectively, harbored frameshift mutations. These mutations were repaired individually, or in combination, using two-step Red mutagenesis. Reconstituted viruses were tested for replication, MD incidence, and their abilities to horizontally spread to contact chickens. The experiments clearly showed that US2, UL13, and gC in combination are essential for horizontal transmission of MDV and that none of the genes alone is able to restore this phenotype.

scholarly journals Antiviral effect of baicalin on Marek’s disease virus in CEF cells

2020 ◽  
Author(s):  
Fan Yang ◽  
Chun Feng ◽  
Yongxiu Yao ◽  
Aijian Qin ◽  
Hongxia Shao ◽  
...  
Keyword(s):  
Disease Virus ◽  
Antiviral Effect ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Virus Infectivity ◽  
Dependent Manner ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Protein Levels ◽  
Anti Oxidant

Abstract Background: Baicalin, the main metabolic component of S.baicalensis Georgi, has various pharmacological properties including anti-inflammatory, anti-oxidant, anti-apoptotic, anti-bactericidal and anti-viral. The purpose of this study was to investigate the anti-Marek’s disease virus (MDV) activities of baicalin in CEF cells.Results: Here, we showed that baicalin could inhibit viral mRNA, protein levels and overall plaque formation in a time-dependent manner. We also found that baicalin could consistently inhibit MDV replication and directly affect the virus infectivity. Moreover, baicalin treatment has no effect on expression level of antiviral cytokine and inflammatory cytokines in virus infected CEFs.Conclusions: These results demonstrate that baicalin could be a potential drug against MDV infection.

scholarly journals Antiviral effect of baicalin on Marek’s disease virus in CEF cells

2020 ◽  
Author(s):  
Fan Yang ◽  
Chun Feng ◽  
Yongxiu Yao ◽  
Aijian Qin ◽  
Hongxia Shao ◽  
...  
Keyword(s):  
Disease Virus ◽  
Antiviral Effect ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Virus Infectivity ◽  
Dependent Manner ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Scutellaria Baicalensis Georgi ◽  
Protein Levels

Abstract Background: Baicalin, the main metabolic component of Scutellaria baicalensis Georgi, has various pharmacological properties including anti-inflammatory, anti-oxidant, anti-apoptotic, anti-bactericidal and anti-viral. The purpose of this study was to investigate the anti-Marek’s disease virus (MDV) activities of baicalin in CEF cells. Results: Here, we showed that baicalin could inhibit viral mRNA, protein levels and overall plaque formation in a time-dependent manner. We also found that baicalin could consistently inhibit MDV replication and directly affect the virus infectivity. Moreover, baicalin treatment has no effect on expression level of antiviral cytokine and inflammatory cytokines in MDV infected CEFs. Conclusions: These results demonstrate that baicalin could be a potential drug against MDV infection.

scholarly journals Antiviral effect of baicalin on Marek’s disease virus in CEF cells

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Fan Yang ◽  
Chun Feng ◽  
Yongxiu Yao ◽  
Aijian Qin ◽  
Hongxia Shao ◽  
...  
Keyword(s):  
Disease Virus ◽  
Antiviral Effect ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Virus Infectivity ◽  
Dependent Manner ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Protein Levels ◽  
Anti Oxidant

Abstract Background Baicalin, the main metabolic component of Scutellaria baicalensis Georgi, has various pharmacological properties including anti-inflammatory, anti-oxidant, anti-apoptotic, anti-bactericidal and anti-viral. The purpose of this study was to investigate the anti-Marek’s disease virus (MDV) activities of baicalin in CEF cells. Results Here, we showed that baicalin could inhibit viral mRNA, protein levels and overall plaque formation in a time-dependent manner. We also found that baicalin could consistently inhibit MDV replication and directly affect the virus infectivity. Moreover, baicalin treatment has no effect on expression level of antiviral cytokine and inflammatory cytokines in MDV infected CEFs. Conclusions These results demonstrate that baicalin could be a potential drug against MDV infection.

scholarly journals Antiviral Effect of Lithium Chloride on Replication of Marek’s Disease Virus in Chicken Embryonic Fibroblasts

2021 ◽  
Vol 22 (22) ◽  
pp. 12375
Author(s):  
Huifeng He ◽  
Dandan Qiao ◽  
Lu Zhang ◽  
Yongxiu Yao ◽  
Hongxia Shao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Disease Virus ◽  
Lithium Chloride ◽  
Antiviral Effect ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Viral Gene ◽  
Dependent Manner ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

To investigate the antiviral effect of lithium chloride (LiCl) on the replication of Marek’s disease virus (MDV) in chicken embryonic fibroblast (CEF) cells, real-time PCR, Western blotting, plaque counting, and indirect immunofluorescence experiments were performed at different time points of LiCl treated CEF cells with virus infection. The results demonstrated that LiCl could affect multiple steps of virus replication and inhibit viral gene expression and protein synthesis in a dose- and time-dependent manner. Moreover, LiCl could directly affect viral infectivity as well. In addition, LiCl significantly affected the gene expression of IFN-β related genes in virus-infected cells. These results indicate that LiCl significantly inhibits MDV replication and proliferation in CEF cells and it has the potential to be used as an antiviral agent against MDV.

Isolation and identification of Marek’s disease virus (MDV) from feather follicle epithelium and internal organs of diseased chickens in Dakahlia Governorate, Egypt

2019 ◽  
Vol 20 (2) ◽  
pp. 6-11
Author(s):  
Aly El-Kenawy ◽  
Mohamed El-Tholoth ◽  
Emad A
Keyword(s):  
Real Time ◽  
Disease Virus ◽  
Real Time Pcr ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Field Samples ◽  
Feather Follicle ◽  
Positive Results

In the present study, a total of 16 samples including feather follicle epithelium, ovary, spleen and kidney (4 samples for each organ) were collected from diseased chicken flocks suspected to be infected with Marek’s disease virus (MDV) at Dakahlia Governorate, Egypt during the period from October 2016 to October 2017. Each sample was pooled randomly from three to five birds (90 to 360 days old). The isolation of the suspected virus from the collected samples was carried out via chorioallantoic membranes (CAMs) of 12 days old embryonated chicken eggs (ECEs). Three egg passages were carried out for each sample. Hyperimmune serum was prepared against standard MDV. MDV in both field and egg passaged samples (after 3rd passage) was identified by agar gel precipitation test (AGPT) and indirect fluorescence antibody test (IFAT). Molecular identification of virus was carried out by conventional polymerase chain reaction (PCR) and real- time PCR in four selected samples. The results revealed that 14 samples (87.5%) including 4 (100%) samples from feather follicle epithelium, ovary and kidney and 2 (50%) samples from spleen, showed positive results in virus isolation after 3rd passage. The positive results percentage by AGPT for field samples were 50% (8 out of 16 samples), while after the 3rd passage in ECEs were 37.5% (6 out of 16 samples) and the positive results percentage by IFAT for field samples were 62.5% (10 out of 16 samples), while after the 3rd passage in ECEs were 81.25 % (13 out of 16 samples). Viral nucleic acid was detected in all selected samples by conventional and real- time PCR. The results indicate that feather follicle epithelium is the best organ for MDV detection. IFAT is superior over AGPT in virus detection. Conventional and real - time PCR could be efficiently used for molecular detection of the virus.

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