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Veterinary Sciences Mar 2024Epigenetic factors, including microRNAs (miRNAs), play an important role in affecting gene expression and, therefore, are involved in various biological processes...
Epigenetic Factor MicroRNAs Likely Mediate Vaccine Protection Efficacy against Lymphomas in Response to Tumor Virus Infection in Chickens through Target Gene Involved Signaling Pathways.
Epigenetic factors, including microRNAs (miRNAs), play an important role in affecting gene expression and, therefore, are involved in various biological processes including immunity protection against tumors. Marek's disease (MD) is a highly contagious disease of chickens caused by the MD virus (MDV). MD has been primarily controlled by vaccinations. MD vaccine efficacy might, in part, be dependent on modulations of a complex set of factors including host epigenetic factors. This study was designed to identify differentially expressed miRNAs in the primary lymphoid organ, bursae of Fabricius, in response to MD vaccination followed by MDV challenge in two genetically divergent inbred lines of White Leghorns. Small RNA sequencing and bioinformatic analyses of the small RNA sequence reads identified hundreds of miRNAs among all the treatment groups. A small portion of the identified miRNAs was differentially expressed within each of the four treatment groups, which were HVT or CVI988/Rispens vaccinated line 6-resistant birds and line 7-susceptible birds. A direct comparison between the resistant line 6 and susceptible line 7 groups vaccinated with HVT followed by MDV challenge identified five differentially expressed miRNAs. Gene Ontology analysis of the target genes of those five miRNAs revealed that those target genes, in addition to various GO terms, are involved in multiple signaling pathways including MAPK, TGF-β, ErbB, and EGFR1 signaling pathways. The general functions of those pathways reportedly play important roles in oncogenesis, anti-cancer immunity, cancer cell migration, and metastatic progression. Therefore, it is highly likely that those miRNAs may, in part, influence vaccine protection through the pathways.
PubMed: 38668407
DOI: 10.3390/vetsci11040139 -
Frontiers in Microbiology 2024Marek's disease virus (MDV) infection causes immunosuppression in the host, ultimately inducing tumor formation and causing significant economic losses to the poultry...
Marek's disease virus (MDV) infection causes immunosuppression in the host, ultimately inducing tumor formation and causing significant economic losses to the poultry industry. While the abnormal activation of the Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors. However, the relationship between MDV and the Wnt/β-catenin pathway remains unclear. In this study, we found that the MDV RB1B strain, but not the MDV vaccine strain CVI988, activated the Wnt/β-catenin signaling pathway by increasing the phosphorylation level of GSK-3β in chicken embryo fibroblast (CEF). infection experiments in SPF chickens also confirmed that the RB1B strain activated the Wnt/β-catenin signaling pathway, while the CVI988 strain did not lead to its activation. Moreover, unlike the Meq protein encoded by the CVI988 strain, the Meq protein encoded by the RB1B strain specifically activated the Wnt/β-catenin signaling pathway in CEF cells. The findings from these studies extend our understanding of the regulation of Wnt/β-catenin signaling by MDV, which make a new contribution to understanding the virus-host interactions of MDV.
PubMed: 38638910
DOI: 10.3389/fmicb.2024.1388862 -
Poultry Science Jun 2024The highly contagious, immunosuppressive, and cancer-causing Marek's disease virus (MDV) infects chickens. The financial costs of Marek's disease (MD) are significant...
The highly contagious, immunosuppressive, and cancer-causing Marek's disease virus (MDV) infects chickens. The financial costs of Marek's disease (MD) are significant for the chicken industry. In this study, a total of 180 samples from chicken farms suspected to be MDV-infected were collected. The chickens were sampled during the period between the months of October 2016 and February 2018 at Dakahlia and Damietta Governorates, Egypt. A total of 36 pooled samples were created. The prepared samples were inoculated into embryonated chicken eggs (ECEs). Indirect fluorescent antibody technique (IFAT) and ICP4 gene-based polymerase chain reaction (PCR) were used for MDV identification. For the genetic characterization of the identified virus, The ICP4 gene sequence was identified and compared with the sequences available from various regions of the world. Furthermore, the genomes of all detected MDVs were screened for the long terminal repeat (LTR) region of reticuloendotheliosis (REV) in their genomes. The results showed that 31 out of 36 pooled samples (86.1%) inoculated into ECEs displayed the characteristic pock lesions. By using IFAT and PCR to identify MDV in ECEs, positive results were found in 27 samples (75%). The Egyptian virus is thought to be genetically closely related to MDVs circulating in Ethiopia, China, and India. REV-LTR was amplified from 6 out of 27 field isolates genomes (22.2 %) while MDV vaccine strains were free from REV-LTR insertion. The integrated REV-LTRs depicted a close genetic relationship with those integrated in fowl poxvirus (FWPV) circulating in Egypt as well as those integrated in FWPVs and MDVs from China, USA, South Africa, and Australia. To the best of our knowledge, this investigation represents the first identification and characterization of REV-LTR insertions in Egyptian MDV field isolates. Given the findings above, additional research in the future seems crucial to determine how the REV-LTR insertions affect MDV pathogenesis, virulence, and insufficient vaccination protection.
Topics: Animals; Marek Disease; Chickens; Egypt; Poultry Diseases; Herpesvirus 2, Gallid; Terminal Repeat Sequences; Reticuloendotheliosis virus; Virus Integration; Genome, Viral
PubMed: 38626691
DOI: 10.1016/j.psj.2024.103722 -
Nature Medicine Apr 2024Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's...
Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab's potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic-rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.
Topics: Humans; Male; Female; Middle Aged; Parkinson Disease; Tremor; Antiparkinson Agents; Monoamine Oxidase; Disease Progression
PubMed: 38622249
DOI: 10.1038/s41591-024-02886-y -
Journal of Nuclear Medicine : Official... Jun 2024We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer...
We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.
Topics: Humans; Positron-Emission Tomography; tau Proteins; Male; Female; Middle Aged; Aged; Phenotype; Pyridines; Tauopathies; Radiopharmaceuticals
PubMed: 38575191
DOI: 10.2967/jnumed.123.265930 -
The Journal of General Virology Apr 2024The herpes simplex virus 1 (HSV1) virion host shutoff (vhs) protein is an endoribonuclease that regulates the translational environment of the infected cell, by inducing...
The herpes simplex virus 1 (HSV1) virion host shutoff (vhs) protein is an endoribonuclease that regulates the translational environment of the infected cell, by inducing the degradation of host mRNA via cellular exonuclease activity. To further understand the relationship between translational shutoff and mRNA decay, we have used ectopic expression to compare HSV1 vhs (vhsH) to its homologues from four other alphaherpesviruses - varicella zoster virus (vhsV), bovine herpesvirus 1 (vhsB), equine herpesvirus 1 (vhsE) and Marek's disease virus (vhsM). Only vhsH, vhsB and vhsE induced degradation of a reporter luciferase mRNA, with poly(A)+ hybridization indicating a global depletion of cytoplasmic poly(A)+ RNA and a concomitant increase in nuclear poly(A)+ RNA and the polyA tail binding protein PABPC1 in cells expressing these variants. By contrast, vhsV and vhsM failed to induce reporter mRNA decay and poly(A)+ depletion, but rather, induced cytoplasmic G3BP1 and poly(A)+ mRNA- containing granules and phosphorylation of the stress response proteins eIF2α and protein kinase R. Intriguingly, regardless of their apparent endoribonuclease activity, all vhs homologues induced an equivalent general blockade to translation as measured by single-cell puromycin incorporation. Taken together, these data suggest that the activities of translational arrest and mRNA decay induced by vhs are separable and we propose that they represent sequential steps of the vhs host interaction pathway.
Topics: Viral Proteins; Ribonucleases; DNA Helicases; Poly-ADP-Ribose Binding Proteins; RNA Helicases; RNA Recognition Motif Proteins; Herpesvirus 1, Human; Endoribonucleases; RNA Stability; Virion; RNA, Messenger
PubMed: 38572740
DOI: 10.1099/jgv.0.001976 -
Endokrynologia Polska 2024Thyroid orbitopathy (TO) is the most common cause of orbital tissue inflammation, accounting for about 60% of all orbital inflammations. The inflammatory activity and...
Thyroid orbitopathy (TO) is the most common cause of orbital tissue inflammation, accounting for about 60% of all orbital inflammations. The inflammatory activity and severity of TO should be diagnosed based on personal experience and according to standard diagnostic criteria. Magnetic resonance imaging (MRI) of the orbit is used not only to identify swelling and to differentiate inflammatory active from non-active TO, but also to exclude other pathologies, such as orbital tumours or vascular lesions. However, a group of diseases can mimic the clinical manifestations of TO, leading to serious diagnostic difficulties, especially when the patient has previously been diagnosed with a thyroid disorder. Diagnostic problems can be presented by cases of unilateral TO, unilateral or bilateral TO in patients with no previous or concomitant symptoms of thyroid disorders, lack of symptoms of eyelid retraction, divergent strabismus, diplopia as the only symptom of the disease, and history of increasing diplopia at the end of the day. The lack of visible efficacy of ongoing immunosuppressive treatment should also raise caution and lead to a differential diagnosis of TO. Differential diagnosis of TO and evaluation of its activity includes conditions leading to redness and/or swelling of the conjunctiva and/or eyelids, and other causes of ocular motility disorders and eye-setting disorders. In this paper, the authors review the most common diseases that can mimic TO or falsify the assessment of inflammatory activity of TO.
Topics: Humans; Graves Ophthalmopathy; Diplopia; Diagnosis, Differential; Orbit; Inflammation
PubMed: 38497384
DOI: 10.5603/ep.98156 -
Frontiers in Veterinary Science 2024Sodium butyrate (NaB) has garnered attention in recent years for its ability to impede the malignant progression of tumors. In order to explore the potential inhibitory...
Sodium butyrate (NaB) has garnered attention in recent years for its ability to impede the malignant progression of tumors. In order to explore the potential inhibitory effects of NaB on the replication of Marek's disease virus (MDV) and subsequent lymphoma formation, newly hatched chickens were infected with the vvMDV Md5 strain and administered NaB prior to (prevention group) or following (treatment group) Md5 inoculation. The results revealed that NaB played a pivotal role in diminishing both the incidence and fatality rates in chickens afflicted with Md5 infection. Notably, NaB exhibited a remarkable capacity to inhibit the expression of MDV immediate early genes, i.e., and , thus attenuating tumorigenesis in the chicken spleen. To further elucidate the mechanism of NaB on lymphoma cells, MDV bearing lymphoma cells, i.e., MSB-1 were exposed to NaB for 24 h prior to various experimental tests. The results revealed that NaB effectively hindered the proliferation, migration, and colony formation of MSB-1 cells. Furthermore, NaB demonstrated the ability to modulate the key molecules in mitochondrial apoptosis pathway. Taken together, these findings reveal that NaB can impede the lymphoma caused by MDV via regulating the mitochondrial apoptosis pathway, both and . These results suggest that the utilization of NaB warrants serious consideration as a promising approach for the prevention of MDV.
PubMed: 38482171
DOI: 10.3389/fvets.2024.1360878 -
The Veterinary Quarterly Dec 2024Marek's disease virus (MDV) has become an increasingly virulent pathogen in the poultry industry despite vaccination efforts to control it. Brazil has experienced a...
Marek's disease virus (MDV) has become an increasingly virulent pathogen in the poultry industry despite vaccination efforts to control it. Brazil has experienced a significant rise of Marek's disease (MD) outbreaks in recent years. Our study aimed to analyze the complete gene sequences to understand the molecular epidemiological basis of MD outbreaks in Brazilian vaccinated layer farms. We detected a high incidence rate of visceral MD (67.74%) and multiple circulating MDV strains. The most prevalent and geographically widespread genotype presented several clinical and molecular characteristics of a highly virulent strain and evolving under positive selective pressure. Phylogenetic and phylogeographic analysis revealed a closer relationship with strains from the USA and Japan. This study sheds light on the circulation of MDV strains capable of infecting vaccinated birds. We emphasize the urgency of adopting preventive measures to manage MDV outbreaks threatening the poultry farming industry.
Topics: Animals; Poultry; Chickens; Brazil; Phylogeny; Mardivirus; Marek Disease; Farms; Oncogenes; Poultry Diseases
PubMed: 38465827
DOI: 10.1080/01652176.2024.2318198 -
Veterinary and Animal Science Mar 2024Marek's disease (MD) and chicken infectious anaemia (CIA) are viral immunosuppressive diseases of poultry caused by the MD virus (MDV) and CIA virus (CIAV) respectively....
Marek's disease (MD) and chicken infectious anaemia (CIA) are viral immunosuppressive diseases of poultry caused by the MD virus (MDV) and CIA virus (CIAV) respectively. Despite vaccination against MD, the incidence of the disease in vaccinated poultry flocks in Nigeria persists. However, underlying factors like co-infection with CIAV have not been investigated in the country. This study was designed to investigate possible co-infections of MDV and CIAV in poultry flocks in Nigeria. In 2016, tumorous tissue samples were collected from suspected cases of MD at necropsy in Jos, Plateau State, Nigeria. The samples collected were fixed in formalin for histopathological examination, genomic DNA was extracted from a second part and analysed by polymerase chain reaction (PCR), targeting the and VP1 genes of the MDV and CIAV, respectively. The histology results revealed that the cutaneous and proventricular lymphomas were characterized by large numbers of mononuclear cellular infiltrates admixed with heterophils. The PCR results revealed that MDV was detected in 66.7% (16/24), CIAV in 45.8% (11/24), and co-infections of MDV and CIAV were detected in 45.8% (11/24) of the samples analysed. In addition, co-infections of MD and CIA were recorded in 100% (6/6) and 27.7% (5/18) of broilers and layer/pullet' samples respectively. Phylogenetic analysis of the gene sequences revealed that the Nigerian MDV clusters with very virulent MDV from Egypt and Italy. While, CIAV sequences were genotype II and genotype III and clustered with CIAVs from Cameroon and China. This is the first report of co-infections of MD and CIA in Nigeria.
PubMed: 38406258
DOI: 10.1016/j.vas.2024.100339