Gallid Alphaherpesvirus 2

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Jun Luo - One of the best experts on this subject based on the ideXlab platform.

  • marek s disease virus Gallid Alphaherpesvirus 2 encoded mir m2 5p simultaneously promotes cell proliferation and suppresses apoptosis through rbm24 and myod1 mediated signaling pathways
    Frontiers in Microbiology, 2020
    Co-Authors: Zhijian Zhu, Man Teng, Luping Zheng, Jinling Liu, Shujun Chai, Yongxiu Yao, Venugopal Nair, Gaiping Zhang, Jun Luo
    Abstract:

    MicroRNAs (miRNAs) have been demonstrated for their involvement in virus biology and pathogenesis, including functioning as key determinants of virally-induced cancers. As an important oncogenic α-herpesvirus affecting poultry health, Marek's disease virus serotype 1 [Gallid Alphaherpesvirus 2 (GaHV-2)] induces rapid-onset T-cell lymphomatous disease commonly referred to as Marek's disease (MD), an excellent biological model for the study of virally-induced cancer in the natural hosts. Previously, we have demonstrated that GaHV-2-encoded miRNAs (especially those within the Meq-cluster) have the potential to act as critical regulators of multiple processes such as virus replication, latency, pathogenesis, and/or oncogenesis. In addition to miR-M4-5p (miR-155 homolog) and miR-M3-5p, we have recently found that miR-M2-5p possibly participate in inducing MD lymphomagenesis. Here, we report the identification of two tumor suppressors, the RNA-binding protein 24 (RBM24) and myogenic differentiation 1 (MYOD1), being two biological targets for miR-M2-5p. Our experiments revealed that as a critical miRNA, miR-M2-5p promotes cell proliferation via regulating the RBM24-mediated p63 overexpression and MYOD1-mediated IGF2 signaling and suppresses apoptosis by targeting the MYOD1-mediated Caspase-3 signaling pathway. Our data present a new strategy of a single viral miRNA exerting dual role to potentially participate in the virally-induced T-cell lymphomagenesis by simultaneously promoting the cell proliferation and suppressing apoptosis.

  • putative roles as oncogene or tumour suppressor of the mid clustered micrornas in Gallid Alphaherpesvirus 2 gahv2 induced marek s disease lymphomagenesis
    Journal of General Virology, 2017
    Co-Authors: Man Teng, Gaiping Zhang, Pu Zhao, Guoqing Zhuang, Lu Dang, Zhizhong Cui, Jun Luo
    Abstract:

    In the last decade, numerous microRNAs (miRNAs) have been identified in diverse virus families, particularly in herpesviruses. Gallid Alphaherpesvirus 2 (GaHV2) is a representative oncogenic Alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts, namely Marek’s disease (MD). In the GaHV2 genome there are 26 mature miRNAs derived from 14 precursors assembled into three clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2 miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been demonstrated to be critical in MD pathogenesis and/or tumorigenesis. Interestingly the downstream Mid-cluster is regulated and transcribed by the same promoter as the Meq-cluster in the latent phase of the infection, but the role of these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated the deletion mutants of the Mid-cluster and of its associated individual miRNAs in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid-clustered miRNAs are not essential for virus replication. Using GaHV2-infected chickens as an animal model, we found that, compared with parental GX0101 virus, the individual deletion of miR-M31 decreased the mortality and gross tumour incidence of infected chickens while the deletion individually of miR-M1 or miR-M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the deletion of the entire Mid-cluster region. More importantly, our data further confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral oncogene meq and suppresses its expression in GaHV2 infection. We report here that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially act either as oncogene or tumour suppressor in MD lymphomagenesis.

  • Dynamic Changes in the Splenic Transcriptome of Chickens during the Early Infection and Progress of Marek’s Disease
    Nature Publishing Group, 2017
    Co-Authors: Lu Dang, Man Teng, Gaiping Zhang, Pu Zhao, Rui-guang Deng, Jun Luo
    Abstract:

    Abstract Gallid Alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek’s disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the ‘Cornell Model’ description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology

  • A Tiny RNA that Packs a Big Punch: The Critical Role of a Viral miR-155 Ortholog in Lymphomagenesis in Marek’s Disease
    Frontiers Media S.A., 2017
    Co-Authors: Guoqing Zhuang, Man Teng, Jun Luo, Aijun Sun
    Abstract:

    MicroRNAs (miRNAs) are small non-coding RNAs that have been identified in animals, plants, and viruses. These small RNAs play important roles in post-transcriptional regulation of various cellular processes, including development, differentiation, and all aspects of cancer biology. Rapid-onset T-cell lymphoma of chickens, namely Marek’s disease (MD), induced by Gallid Alphaherpesvirus 2 (GaHV2), could provide an ideal natural animal model for herpesvirus-related cancer research. GaHV2 encodes 26 mature miRNAs derived from 14 precursors assembled in three distinct gene clusters in the viral genome. One of the most highly expressed GaHV2 miRNAs, miR-M4-5p, shows high sequence similarity to the cellular miR-155 and the miR-K12-11 encoded by Kaposi’s sarcoma-associated herpesvirus, particularly in the miRNA “seed region.” As with miR-K12-11, miR-M4-5p shares a common set of host and viral target genes with miR-155, suggesting that they may target the same regulatory cellular networks; however, differences in regulatory function between miR-155 and miR-M4-5p may distinguish non-viral and viral mediated tumorigenesis. In this review, we focus on the functions of miR-M4-5p as the viral ortholog of miR-155 to explore how the virus mimics a host pathway to benefit the viral life cycle and trigger virus-induced tumorigenesis

Elena Catelli - One of the best experts on this subject based on the ideXlab platform.

  • marek s disease viruses circulating in commercial poultry in italy in the years 2015 2018 are closely related by their meq gene phylogeny
    Transboundary and Emerging Diseases, 2020
    Co-Authors: Giulia Mescolini, Caterina Lupini, Irit Davidson, Paola Massi, Giovanni Tosi, Elena Catelli
    Abstract:

    Marek's disease (MD) is a lymphoproliferative disease important to the poultry industry worldwide; it is caused by Gallid Alphaherpesvirus 2 (GaHV-2). The virulence of GaHV-2 isolates has shifted over the years from mild to virulent, very virulent and very virulent +. Nowadays the disease is controlled by vaccination, but field strains of increased virulence are emerging worldwide. Economic losses due to MD are mostly associated with its acute form, characterized by visceral lymphomas. The present study aimed to molecularly classify a group of 13 GaHV-2 strains detected in vaccinated Italian commercial chicken flocks during acute MD outbreaks, and to scrutinize the ability of predicting GaHV-2 virulence, according to the meq gene sequence. The full-length meq genes were amplified, and the obtained amino acid (aa) sequences were analysed, focusing mainly on the number of stretches of four proline molecules (PPPP) within the transactivation domain. Phylogenetic analysis was carried out with the Maximum Likelihood method using the obtained aa sequences, and the sequences of Italian strains detected in backyard flocks and of selected strains retrieved from GenBank. All the analysed strains showed 100% sequence identity in the meq gene, which encodes a Meq protein of 339 aa. The Meq protein includes four PPPP motifs in the transactivation domain and an interruption of a PPPP motif due to a proline-to-serine substitution at position 218. These features are typically encountered in highly virulent isolates. Phylogenetic analysis revealed that the analysed strains belonged to a cluster that includes high-virulence GaHV-2 strains detected in Italian backyard flocks and a hypervirulent Polish strain. Our results support the hypothesis that the virulence of field isolates can be suggested by meq aa sequence analysis.

Gaiping Zhang - One of the best experts on this subject based on the ideXlab platform.

  • marek s disease virus Gallid Alphaherpesvirus 2 encoded mir m2 5p simultaneously promotes cell proliferation and suppresses apoptosis through rbm24 and myod1 mediated signaling pathways
    Frontiers in Microbiology, 2020
    Co-Authors: Zhijian Zhu, Man Teng, Luping Zheng, Jinling Liu, Shujun Chai, Yongxiu Yao, Venugopal Nair, Gaiping Zhang, Jun Luo
    Abstract:

    MicroRNAs (miRNAs) have been demonstrated for their involvement in virus biology and pathogenesis, including functioning as key determinants of virally-induced cancers. As an important oncogenic α-herpesvirus affecting poultry health, Marek's disease virus serotype 1 [Gallid Alphaherpesvirus 2 (GaHV-2)] induces rapid-onset T-cell lymphomatous disease commonly referred to as Marek's disease (MD), an excellent biological model for the study of virally-induced cancer in the natural hosts. Previously, we have demonstrated that GaHV-2-encoded miRNAs (especially those within the Meq-cluster) have the potential to act as critical regulators of multiple processes such as virus replication, latency, pathogenesis, and/or oncogenesis. In addition to miR-M4-5p (miR-155 homolog) and miR-M3-5p, we have recently found that miR-M2-5p possibly participate in inducing MD lymphomagenesis. Here, we report the identification of two tumor suppressors, the RNA-binding protein 24 (RBM24) and myogenic differentiation 1 (MYOD1), being two biological targets for miR-M2-5p. Our experiments revealed that as a critical miRNA, miR-M2-5p promotes cell proliferation via regulating the RBM24-mediated p63 overexpression and MYOD1-mediated IGF2 signaling and suppresses apoptosis by targeting the MYOD1-mediated Caspase-3 signaling pathway. Our data present a new strategy of a single viral miRNA exerting dual role to potentially participate in the virally-induced T-cell lymphomagenesis by simultaneously promoting the cell proliferation and suppressing apoptosis.

  • putative roles as oncogene or tumour suppressor of the mid clustered micrornas in Gallid Alphaherpesvirus 2 gahv2 induced marek s disease lymphomagenesis
    Journal of General Virology, 2017
    Co-Authors: Man Teng, Gaiping Zhang, Pu Zhao, Guoqing Zhuang, Lu Dang, Zhizhong Cui, Jun Luo
    Abstract:

    In the last decade, numerous microRNAs (miRNAs) have been identified in diverse virus families, particularly in herpesviruses. Gallid Alphaherpesvirus 2 (GaHV2) is a representative oncogenic Alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts, namely Marek’s disease (MD). In the GaHV2 genome there are 26 mature miRNAs derived from 14 precursors assembled into three clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2 miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been demonstrated to be critical in MD pathogenesis and/or tumorigenesis. Interestingly the downstream Mid-cluster is regulated and transcribed by the same promoter as the Meq-cluster in the latent phase of the infection, but the role of these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated the deletion mutants of the Mid-cluster and of its associated individual miRNAs in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid-clustered miRNAs are not essential for virus replication. Using GaHV2-infected chickens as an animal model, we found that, compared with parental GX0101 virus, the individual deletion of miR-M31 decreased the mortality and gross tumour incidence of infected chickens while the deletion individually of miR-M1 or miR-M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the deletion of the entire Mid-cluster region. More importantly, our data further confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral oncogene meq and suppresses its expression in GaHV2 infection. We report here that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially act either as oncogene or tumour suppressor in MD lymphomagenesis.

  • Dynamic Changes in the Splenic Transcriptome of Chickens during the Early Infection and Progress of Marek’s Disease
    Nature Publishing Group, 2017
    Co-Authors: Lu Dang, Man Teng, Gaiping Zhang, Pu Zhao, Rui-guang Deng, Jun Luo
    Abstract:

    Abstract Gallid Alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek’s disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the ‘Cornell Model’ description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology

Man Teng - One of the best experts on this subject based on the ideXlab platform.

  • marek s disease virus Gallid Alphaherpesvirus 2 encoded mir m2 5p simultaneously promotes cell proliferation and suppresses apoptosis through rbm24 and myod1 mediated signaling pathways
    Frontiers in Microbiology, 2020
    Co-Authors: Zhijian Zhu, Man Teng, Luping Zheng, Jinling Liu, Shujun Chai, Yongxiu Yao, Venugopal Nair, Gaiping Zhang, Jun Luo
    Abstract:

    MicroRNAs (miRNAs) have been demonstrated for their involvement in virus biology and pathogenesis, including functioning as key determinants of virally-induced cancers. As an important oncogenic α-herpesvirus affecting poultry health, Marek's disease virus serotype 1 [Gallid Alphaherpesvirus 2 (GaHV-2)] induces rapid-onset T-cell lymphomatous disease commonly referred to as Marek's disease (MD), an excellent biological model for the study of virally-induced cancer in the natural hosts. Previously, we have demonstrated that GaHV-2-encoded miRNAs (especially those within the Meq-cluster) have the potential to act as critical regulators of multiple processes such as virus replication, latency, pathogenesis, and/or oncogenesis. In addition to miR-M4-5p (miR-155 homolog) and miR-M3-5p, we have recently found that miR-M2-5p possibly participate in inducing MD lymphomagenesis. Here, we report the identification of two tumor suppressors, the RNA-binding protein 24 (RBM24) and myogenic differentiation 1 (MYOD1), being two biological targets for miR-M2-5p. Our experiments revealed that as a critical miRNA, miR-M2-5p promotes cell proliferation via regulating the RBM24-mediated p63 overexpression and MYOD1-mediated IGF2 signaling and suppresses apoptosis by targeting the MYOD1-mediated Caspase-3 signaling pathway. Our data present a new strategy of a single viral miRNA exerting dual role to potentially participate in the virally-induced T-cell lymphomagenesis by simultaneously promoting the cell proliferation and suppressing apoptosis.

  • putative roles as oncogene or tumour suppressor of the mid clustered micrornas in Gallid Alphaherpesvirus 2 gahv2 induced marek s disease lymphomagenesis
    Journal of General Virology, 2017
    Co-Authors: Man Teng, Gaiping Zhang, Pu Zhao, Guoqing Zhuang, Lu Dang, Zhizhong Cui, Jun Luo
    Abstract:

    In the last decade, numerous microRNAs (miRNAs) have been identified in diverse virus families, particularly in herpesviruses. Gallid Alphaherpesvirus 2 (GaHV2) is a representative oncogenic Alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts, namely Marek’s disease (MD). In the GaHV2 genome there are 26 mature miRNAs derived from 14 precursors assembled into three clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2 miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been demonstrated to be critical in MD pathogenesis and/or tumorigenesis. Interestingly the downstream Mid-cluster is regulated and transcribed by the same promoter as the Meq-cluster in the latent phase of the infection, but the role of these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated the deletion mutants of the Mid-cluster and of its associated individual miRNAs in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid-clustered miRNAs are not essential for virus replication. Using GaHV2-infected chickens as an animal model, we found that, compared with parental GX0101 virus, the individual deletion of miR-M31 decreased the mortality and gross tumour incidence of infected chickens while the deletion individually of miR-M1 or miR-M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the deletion of the entire Mid-cluster region. More importantly, our data further confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral oncogene meq and suppresses its expression in GaHV2 infection. We report here that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially act either as oncogene or tumour suppressor in MD lymphomagenesis.

  • Dynamic Changes in the Splenic Transcriptome of Chickens during the Early Infection and Progress of Marek’s Disease
    Nature Publishing Group, 2017
    Co-Authors: Lu Dang, Man Teng, Gaiping Zhang, Pu Zhao, Rui-guang Deng, Jun Luo
    Abstract:

    Abstract Gallid Alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek’s disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the ‘Cornell Model’ description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology

  • A Tiny RNA that Packs a Big Punch: The Critical Role of a Viral miR-155 Ortholog in Lymphomagenesis in Marek’s Disease
    Frontiers Media S.A., 2017
    Co-Authors: Guoqing Zhuang, Man Teng, Jun Luo, Aijun Sun
    Abstract:

    MicroRNAs (miRNAs) are small non-coding RNAs that have been identified in animals, plants, and viruses. These small RNAs play important roles in post-transcriptional regulation of various cellular processes, including development, differentiation, and all aspects of cancer biology. Rapid-onset T-cell lymphoma of chickens, namely Marek’s disease (MD), induced by Gallid Alphaherpesvirus 2 (GaHV2), could provide an ideal natural animal model for herpesvirus-related cancer research. GaHV2 encodes 26 mature miRNAs derived from 14 precursors assembled in three distinct gene clusters in the viral genome. One of the most highly expressed GaHV2 miRNAs, miR-M4-5p, shows high sequence similarity to the cellular miR-155 and the miR-K12-11 encoded by Kaposi’s sarcoma-associated herpesvirus, particularly in the miRNA “seed region.” As with miR-K12-11, miR-M4-5p shares a common set of host and viral target genes with miR-155, suggesting that they may target the same regulatory cellular networks; however, differences in regulatory function between miR-155 and miR-M4-5p may distinguish non-viral and viral mediated tumorigenesis. In this review, we focus on the functions of miR-M4-5p as the viral ortholog of miR-155 to explore how the virus mimics a host pathway to benefit the viral life cycle and trigger virus-induced tumorigenesis

Catelli E. - One of the best experts on this subject based on the ideXlab platform.

  • Molecular characterization of a Marek's disease virus strain detected in tumour-bearing turkeys
    'Informa UK Limited', 2020
    Co-Authors: Mescolini G., Lupini C., Massi P., Tosi G., Fiorentini L., Catelli E.
    Abstract:

    Marek's disease (MD) is a lymphoproliferative disease caused by Gallid Alphaherpesvirus 2 (GaHV-2), which primarily affects chickens. However, the virus is also able to induce tumours in turkeys, albeit less frequently than in chickens. This study reports the molecular characterization of a GaHV-2 strain detected in a flock of Italian meat-type turkeys exhibiting visceral lymphomas. Sequencing and phylogenetic analysis of the meq gene revealed that the turkey GaHV-2 has molecular features of high virulence and genetic similarity with GaHV-2 strains recently detected in Italian commercial and backyard chickens. GaHV-2 is ubiquitous among chickens despite vaccination, and chicken-to-turkey transmission is hypothesized due to the presence of broilers in neighbouring pens

  • Marek's disease viruses circulating in commercial poultry in Italy in the years 2015\u20132018 are closely related by their meq gene phylogeny
    'Wiley', 2020
    Co-Authors: Mescolini G., Lupini C., Massi P., Tosi G., Catelli E.
    Abstract:

    Marek's disease (MD) is a lymphoproliferative disease important to the poultry industry worldwide; it is caused by Gallid Alphaherpesvirus 2 (GaHV-2). The virulence of GaHV-2 isolates has shifted over the years from mild to virulent, very virulent and very virulent +. Nowadays the disease is controlled by vaccination, but field strains of increased virulence are emerging worldwide. Economic losses due to MD are mostly associated with its acute form, characterized by visceral lymphomas. The present study aimed to molecularly classify a group of 13 GaHV-2 strains detected in vaccinated Italian commercial chicken flocks during acute MD outbreaks, and to scrutinize the ability of predicting GaHV-2 virulence, according to the meq gene sequence. The full-length meq genes were amplified, and the obtained amino acid (aa) sequences were analysed, focusing mainly on the number of stretches of four proline molecules (PPPP) within the transactivation domain. Phylogenetic analysis was carried out with the Maximum Likelihood method using the obtained aa sequences, and the sequences of Italian strains detected in backyard flocks and of selected strains retrieved from GenBank. All the analysed strains showed 100% sequence identity in the meq gene, which encodes a Meq protein of 339 aa. The Meq protein includes four PPPP motifs in the transactivation domain and an interruption of a PPPP motif due to a proline-to-serine substitution at position 218. These features are typically encountered in highly virulent isolates. Phylogenetic analysis revealed that the analysed strains belonged to a cluster that includes high-virulence GaHV-2 strains detected in Italian backyard flocks and a hypervirulent Polish strain. Our results support the hypothesis that the virulence of field isolates can be suggested by meq aa sequence analysis

  • Molecular characterization of Marek217;s disease virus detected in backyard chickens affected by classical nervous form.
    2017
    Co-Authors: Mescolini G., Lupini C., Silveira F., Cecchinato Mattia, Di Francesco A., Catelli E.
    Abstract:

    Marek\u2019s disease (MD) is a worldwide, contagious, lymphoprolipherative disease of chicken caused by a lymphotropic and oncogenic virus, Gallid Alphaherpesvirus 2, also known as Marek\u2019s Disease Virus serotype 1 (MDV-1). MDV-1 can cause neoplastic (lymphomas) and non neoplastic (neurological syndromes and immunosuppression) pathological syndromes. The nervous syndrome characterized mainly by peripheral nerve lesions accompanied by spastic paralysis of legs is termed classical MD. An outbreak of classical MD in unvaccinated Cochin chickens from an Italian backyard flock is reported. After suppression two birds, showing inability to stand upright and spastic paralysis of legs, were necropsied and organs were taken for histologic examination and molecular analysis. MDV-1 was detected from feathers and organs by PCR targeting the meq gene. Meq gene of the detected strain was fully sequenced along with commercial vaccines most commonly used in Italy. Using BioEdit Sequence Alignment Editor, nucleotide and amino acid sequences were edited and compared to meq sequences of selected MDV-1 reference strains, retrieved from GenBank, having different degrees of pathogenicity. Phylogenetic analysis of the amino acid sequences was performed using neighbor- joining clustering method. The high number of PPPP repeats found in the transactivation domain of the Meq protein and the phylogenetic tree obtained showed that the detected virus was closely related to mild or attenuated MDV-1 strains, but different from the analyzed vaccines. The molecular results were supported by clinical, macroscopic and microscopic findings. A- and B-type lesions, highly suggestive of a mild MDV- 1 infection, were observed in enlarged peripheral nerves (brachial plexus, lumbosacral plexus and sciatic, vagus and intercostal nerves). Major Histocompatibility Complex (MHC) haplotype B19, known to be correlated with high susceptibility to Marek\u2019s disease, was identified in affected chickens by PCR and sequencing of B-L II family genes. Because sequencing of the meq gene is not a sufficient criteria to determine the pathotype, virus isolation will be attempted in order to confirm the molecular results by in vivo experimental trials