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Article: Latest Insights into Unique Open Reading Frames Encoded by Unique Long (UL) and Short (US) Regions of Marek’s Disease Virus

Liao, Yifei / Lupiani, Blanca / Reddy, Sanjay M.

Viruses. 2021 May 25, v. 13, no. 6

2021

Abstract: Marek’s disease virus (MDV) is an oncogenic avian alphaherpesvirus whose genome consists of unique long (UL) and short (US) regions that are flanked by inverted repeat regions. More than 100 open reading frames (ORFs) have been annotated in the MDV ... ...

Abstract	Marek’s disease virus (MDV) is an oncogenic avian alphaherpesvirus whose genome consists of unique long (UL) and short (US) regions that are flanked by inverted repeat regions. More than 100 open reading frames (ORFs) have been annotated in the MDV genome, and are involved in various aspects of MDV biology and pathogenesis. Within UL and US regions of MDV, there are several unique ORFs, some of which have recently been shown to be important for MDV replication and pathogenesis. In this review, we will summarize the current knowledge on these ORFs and compare their location in different MDV strains.
Keywords	birds ; genome ; pathogenesis
Language	English
Dates of publication	2021-0525
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13060974
Database	NAL-Catalogue (AGRICOLA)

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

Liao, Yifei / Lupiani, Blanca / Reddy, Sanjay M

Microorganisms. 2021 Mar. 26, v. 9, no. 4

2021

Abstract: 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 ... ...

Abstract	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.
Keywords	fluorescent antibody technique ; gene expression ; leukemia ; lymphatic diseases ; proteasome endopeptidase complex ; proteasome inhibitors ; serine ; threonine
Language	English
Dates of publication	2021-0326
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9040685
Database	NAL-Catalogue (AGRICOLA)

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Article: Manipulation of Promyelocytic Leukemia Protein Nuclear Bodies by Marek's Disease Virus Encoded US3 Protein Kinase.

Liao, Yifei / Lupiani, Blanca / Reddy, Sanjay M

Microorganisms

2021 Volume 9, Issue 4

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2021-03-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9040685
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Latest Insights into Unique Open Reading Frames Encoded by Unique Long (UL) and Short (US) Regions of Marek's Disease Virus.

Liao, Yifei / Lupiani, Blanca / Reddy, Sanjay M

Viruses

2021 Volume 13, Issue 6

Abstract: Marek's disease virus (MDV) is an oncogenic avian alphaherpesvirus whose genome consists of unique long (UL) and short (US) regions that are flanked by inverted repeat regions. More than 100 open reading frames (ORFs) have been annotated in the MDV ... ...

Abstract	Marek's disease virus (MDV) is an oncogenic avian alphaherpesvirus whose genome consists of unique long (UL) and short (US) regions that are flanked by inverted repeat regions. More than 100 open reading frames (ORFs) have been annotated in the MDV genome, and are involved in various aspects of MDV biology and pathogenesis. Within UL and US regions of MDV, there are several unique ORFs, some of which have recently been shown to be important for MDV replication and pathogenesis. In this review, we will summarize the current knowledge on these ORFs and compare their location in different MDV strains.
MeSH term(s)	Animals ; Chickens/virology ; DNA, Viral/genetics ; Genome, Viral ; Herpesvirus 2, Gallid/genetics ; Marek Disease/virology ; Open Reading Frames ; Viral Proteins/genetics ; Virus Replication
Chemical Substances	DNA, Viral ; Viral Proteins
Language	English
Publishing date	2021-05-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13060974
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Methods for the Manipulation of Herpesvirus Genome and the Application to Marek's Disease Virus Research.

Liao, Yifei / Bajwa, Kanika / Reddy, Sanjay M / Lupiani, Blanca

Microorganisms

2021 Volume 9, Issue 6

Abstract: Herpesviruses are a group of double-strand DNA viruses that infect a wide range of hosts, including humans and animals. In the past decades, numerous methods have been developed to manipulate herpesviruses genomes, from the introduction of random ... ...

Abstract	Herpesviruses are a group of double-strand DNA viruses that infect a wide range of hosts, including humans and animals. In the past decades, numerous methods have been developed to manipulate herpesviruses genomes, from the introduction of random mutations to specific genome editing. The development of genome manipulation methods has largely advanced the study of viral genes function, contributing not only to the understanding of herpesvirus biology and pathogenesis, but also the generation of novel vaccines and therapies to control and treat diseases. In this review, we summarize the major methods of herpesvirus genome manipulation with emphasis in their application to Marek's disease virus research.
Language	English
Publishing date	2021-06-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9061260
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Marek's disease virus US3 protein kinase phosphorylates chicken HDAC 1 and 2 and regulates viral replication and pathogenesis.

Liao, Yifei / Lupiani, Blanca / Ai-Mahmood, Mohammad / Reddy, Sanjay M

PLoS pathogens

2021 Volume 17, Issue 2, Page(s) e1009307

Abstract: 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 ...

Abstract	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 an 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 HDAC 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.
MeSH term(s)	Animals ; Chickens ; Herpesvirus 2, Gallid/pathogenicity ; Histone Deacetylase 1/genetics ; Histone Deacetylase 1/metabolism ; Histone Deacetylase 2/genetics ; Histone Deacetylase 2/metabolism ; Marek Disease/metabolism ; Marek Disease/pathology ; Marek Disease/virology ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
Chemical Substances	Viral Proteins ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Histone Deacetylase 1 (EC 3.5.1.98) ; Histone Deacetylase 2 (EC 3.5.1.98)
Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.1009307
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Marek's disease virus Meq oncoprotein interacts with chicken HDAC 1 and 2 and mediates their degradation via proteasome dependent pathway.

Liao, Yifei / Lupiani, Blanca / Izumiya, Yoshihiro / Reddy, Sanjay M

Scientific reports

2021 Volume 11, Issue 1, Page(s) 637

Abstract: Marek's disease virus (MDV) encodes a basic-leucine zipper (BZIP) protein, Meq, which is considered the major MDV oncoprotein. It has been reported that the oncogenicity of Meq is associated with its interaction with C-terminal binding protein 1 (CtBP), ... ...

Abstract	Marek's disease virus (MDV) encodes a basic-leucine zipper (BZIP) protein, Meq, which is considered the major MDV oncoprotein. It has been reported that the oncogenicity of Meq is associated with its interaction with C-terminal binding protein 1 (CtBP), which is also an interaction partner of Epstein-Barr virus encoded EBNA3A and EBNA3C oncoproteins. Since both EBNA3C and CtBP interact with histone deacetylase 1 (HDAC1) and HDAC2, we examined whether Meq shares this interaction with chicken HDAC1 (chHDAC1) and chHDAC2. Using confocal microscopy analysis, we show that Meq co-localizes with chHDAC1 and chHDAC2 in the nuclei of MDV lymphoblastoid tumor cells. In addition, immunoprecipitation assays demonstrate that Meq interacts with chHDAC1 and chHDAC2 in transfected cells and MDV lymphoblastoid tumor cells. Using deletion mutants, interaction domains were mapped to the N-terminal dimerization domain of chHDAC1 and chHDAC2, and the BZIP domain of Meq. Our results further demonstrate that this interaction mediates the degradation of chHDAC1 and chHDAC2 via the proteasome dependent pathway. In addition, our results show that Meq also induces the reduction of global ubiquitinated proteins through a proteasome dependent pathway. In conclusion, our results provide evidence that Meq interacts with chHDAC1 and chHDAC2, and induces their proteasome dependent degradation.
MeSH term(s)	Animals ; Chickens ; Herpesvirus 2, Gallid/isolation & purification ; Histone Deacetylase 1/genetics ; Histone Deacetylase 1/metabolism ; Histone Deacetylase 2/genetics ; Histone Deacetylase 2/metabolism ; Humans ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/pathology ; Kidney Neoplasms/virology ; Lymphoma/metabolism ; Lymphoma/pathology ; Lymphoma/virology ; Marek Disease/complications ; Marek Disease/metabolism ; Marek Disease/pathology ; Marek Disease/virology ; Oncogene Proteins, Viral/genetics ; Oncogene Proteins, Viral/metabolism ; Poultry Diseases/metabolism ; Poultry Diseases/pathology ; Poultry Diseases/virology ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis
Chemical Substances	Eco-Q protein, Gallid herpesvirus 2 ; Oncogene Proteins, Viral ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Histone Deacetylase 1 (EC 3.5.1.98) ; Histone Deacetylase 2 (EC 3.5.1.98)
Language	English
Publishing date	2021-01-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-80792-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Phenotypic Characterization of Recombinant Marek's Disease Virus in Live Birds Validates Polymorphisms Associated with Virulence.

Kim, Taejoong / Hearn, Cari J / Mays, Jody / Velez-Irizarry, Deborah / Reddy, Sanjay M / Spatz, Stephen J / Cheng, Hans H / Dunn, John R

Viruses

2023 Volume 15, Issue 11

Abstract: Marek's disease (MD) is a highly infectious lymphoproliferative disease in chickens with a significant economic impact. ...

Abstract	Marek's disease (MD) is a highly infectious lymphoproliferative disease in chickens with a significant economic impact.
MeSH term(s)	Animals ; Marek Disease ; Virulence/genetics ; Chickens ; Herpesvirus 2, Gallid/genetics ; Mardivirus/genetics
Language	English
Publishing date	2023-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15112263
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Methods for the Manipulation of Herpesvirus Genome and the Application to Marek’s Disease Virus Research

Liao, Yifei / Bajwa, Kanika / Reddy, Sanjay M. / Lupiani, Blanca

Microorganisms. 2021 June 10, v. 9, no. 6

2021

Abstract	Herpesviruses are a group of double-strand DNA viruses that infect a wide range of hosts, including humans and animals. In the past decades, numerous methods have been developed to manipulate herpesviruses genomes, from the introduction of random mutations to specific genome editing. The development of genome manipulation methods has largely advanced the study of viral genes function, contributing not only to the understanding of herpesvirus biology and pathogenesis, but also the generation of novel vaccines and therapies to control and treat diseases. In this review, we summarize the major methods of herpesvirus genome manipulation with emphasis in their application to Marek’s disease virus research.
Keywords	Mardivirus ; disease control ; gene editing ; genes ; host range ; humans ; microorganisms ; mutation ; pathogenesis ; therapeutics ; vaccines
Language	English
Dates of publication	2021-0610
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9061260
Database	NAL-Catalogue (AGRICOLA)

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Article: US3 Serine/Threonine Protein Kinase from MDV-1, MDV-2, and HVT Differentially Regulate Viral Gene Expression and Replication

Liao, Yifei / Fang, Xin / AI-Mahmood, Mohammad / Li, Qinglei / Lupiani, Blanca / Reddy, Sanjay M

Microorganisms. 2021 Apr. 09, v. 9, no. 4

2021

Abstract: Gallid alphaherpesvirus 2 (GaHV-2), commonly known as Marek’s disease virus type 1 (MDV-1), is an oncogenic avian alphaherpesvirus, and along with its close relatives—Gallid alphaherpesvirus 3 (GaHV-3) or MDV-2 and Meleagrid alphaherpesvirus 1 (MeHV-1) ... ...

Abstract	Gallid alphaherpesvirus 2 (GaHV-2), commonly known as Marek’s disease virus type 1 (MDV-1), is an oncogenic avian alphaherpesvirus, and along with its close relatives—Gallid alphaherpesvirus 3 (GaHV-3) or MDV-2 and Meleagrid alphaherpesvirus 1 (MeHV-1) or turkey herpesvirus (HVT)—belongs to the Mardivirus genus. We and others previously showed that MDV-1 US3 protein kinase plays an important role in viral replication and pathogenesis, which could be partially compensated by MDV-2 and HVT US3. In this study, we further studied the differential roles of MDV-1, MDV-2 and HVT US3 in regulating viral gene expression and replication. Our results showed that MDV-2 and HVT US3 could differentially compensate MDV-1 US3 regulation of viral gene expression in vitro. MDV-2 and HVT US3 could also partially rescue the replication deficiency of MDV-1 US3 null virus in the spleen and thymus, as determined by immunohistochemistry analysis of MDV-1 pp38 protein. Importantly, using immunohistochemistry and dual immunofluorescence assays, we found that MDV-2 US3, but not HVT US3, fully compensated MDV-1 US3 regulation of MDV-1 replication in bursal B lymphocytes. In conclusion, our study provides the first comparative analysis of US3 from MDV-1, MDV-2 and HVT in regulating viral gene expression in cell culture and MDV-1 replication in lymphocytes.
Keywords	Gallid alphaherpesvirus 2 ; Meleagrid alphaherpesvirus 1 ; birds ; cell culture ; fluorescent antibody technique ; gene expression ; immunohistochemistry ; pathogenesis ; serine ; spleen ; threonine ; virus replication ; viruses
Language	English
Dates of publication	2021-0409
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9040785
Database	NAL-Catalogue (AGRICOLA)

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