-
Science China. Life Sciences Feb 2023Over the past two decades, numerous non-coding RNAs (ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses... (Review)
Review
Over the past two decades, numerous non-coding RNAs (ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses such as herpesviruses. As a representative oncogenic alphaherpesvirus, Marek's disease virus (MDV) causes an important immunosuppressive and rapid-onset neoplastic disease of poultry, namely Marek's disease (MD). Vaccinations can efficiently prevent the onset of MD lymphomas and other clinical disease, often heralded as the first successful example of vaccination-based control of cancer. MDV infection is also an excellent model for research into virally-induced tumorigenesis. Recently, great progress has been made in understanding the functions of ncRNAs in MD biology. Herein, we give a review of the discovery and identification of MDV-encoded viral miRNAs, focusing on the genomics, expression profiles, and emerging critical roles of MDV-1 miRNAs as oncogenic miRNAs (oncomiRs) or tumor suppressor genes involved in the induction of MD lymphomas. We also described the involvements of host cellular miRNAs, lincRNAs, and circRNAs participating in MDV life cycle, pathogenesis, and/or tumorigenesis. The prospects, strategies, and new techniques such as the CRISPR/Cas9-based gene editing applicable for further investigation into the ncRNA-mediated regulatory mechanisms in MDV pathogenesis/oncogenesis were also discussed, together with the possibilities of future studies on antiviral therapy and the development of new efficient MD vaccines.
Topics: Animals; Cell Transformation, Neoplastic; Chickens; Herpesvirus 2, Gallid; Lymphoma; Marek Disease; MicroRNAs
PubMed: 36617590
DOI: 10.1007/s11427-022-2258-4 -
Virulence Dec 2022Co-infection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) synergistically drives disease progression, yet little is known about the mechanism of...
Co-infection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) synergistically drives disease progression, yet little is known about the mechanism of the synergism. Here, we found that co-infection of REV and MDV increased their replication via the RIOK3-Akt pathway. Initially, we noticed that the viral titres of MDV and REV significantly increased in REV and MDV co-infected cells compared with single-infected cells. Furthermore, tandem mass tag peptide labelling coupled with LC/MS analysis showed that Akt was upregulated in REV and MDV co-infected cells. Overexpression of Akt promoted synergistic replication of MDV and REV. Conversely, inhibition of Akt suppressed synergistic replication of MDV and REV. However, PI3K inhibition did not affect synergistic replication of MDV and REV, suggesting that the PI3K/Akt pathway is not involved in the synergism of MDV and REV. In addition, we revealed that RIOK3 was recruited to regulate Akt in REV and MDV co-infected cells. Moreover, wild-type RIOK3, but not kinase-dead RIOK3, mediated Akt phosphorylation and promoted synergistic replication of MDV and REV. Our results illustrate that MDV and REV activated a novel RIOK3-Akt signalling pathway to facilitate their synergistic replication.
Topics: Animals; Chickens; Coinfection; Genetic Diseases, X-Linked; Herpesvirus 2, Gallid; Humans; Marek Disease; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Reticuloendotheliosis virus; Severe Combined Immunodeficiency; Virus Replication
PubMed: 35795905
DOI: 10.1080/21505594.2022.2096247 -
Microbial Pathogenesis Sep 2022Marek's disease virus (MDV), a highly contagious cell associated virus, is the etiological agent of Marek's disease (MD), a lymphoproliferative and neuropathic disease...
Marek's disease virus (MDV), a highly contagious cell associated virus, is the etiological agent of Marek's disease (MD), a lymphoproliferative and neuropathic disease of domestic chickens. Clinical signs of MD include transient paralysis, bursal/thymic atrophy, and T cell lymphomas. MicroRNAs (miRNAs) are short single-stranded non-coding RNAs that regulate gene expression by transcriptional suppression or mRNA degradation. Herpesviruses, including MDV, encode for miRNAs that are known to play essential roles in viral pathogenicity, oncogenesis, and evasion of immune responses. In this study, we performed miRNA sequencing in thymuses of control and MDV-infected chickens of MD-resistant (6) and susceptible (7) lines at 21 days post infection (dpi). The thymus is a lymphoid organ that undergoes severe atrophy due to MDV-induced apoptotic mediated destruction of T cells. Sequence analysis identified 658 total chicken miRNAs in the thymuses of control and MDV-infected birds of both lines. Of these, 453 were novel and 205 were known microRNAs. All novel miRNAs mapped to chicken genome with no sequence homology to existing miRNAs in the chicken miRbase. Comparative analysis between the thymuses of control and infected birds of resistant and susceptible lines identified 78 differentially expressed microRNAs that might provide insights into mechanisms of thymus atrophy.
Topics: Animals; Atrophy; Chickens; Marek Disease; MicroRNAs; T-Lymphocytes
PubMed: 35917989
DOI: 10.1016/j.micpath.2022.105688 -
International Journal of Molecular... Apr 2020Although gene-environment interactions are known to play an important role in the inheritance of complex traits, it is still unknown how a genotype and the environmental... (Review)
Review
Although gene-environment interactions are known to play an important role in the inheritance of complex traits, it is still unknown how a genotype and the environmental factors result in an observable phenotype. Understanding this complex interaction in the pathogenesis of diabetic retinopathy (DR) remains a big challenge as DR appears to be a disease with heterogenous phenotypes with multifactorial influence. In this review, we examine the natural history and risk factors related to DR, emphasizing distinct clinical phenotypes and their natural course in retinopathy. Although there is strong evidence that duration of diabetes and metabolic factors play a key role in the pathogenesis of DR, accumulating new clinical studies reveal that this disease can develop independently of duration of diabetes and metabolic dysfunction. More recently, studies have emphasized the role of genetic factors in DR. However, linkage analyses, candidate gene studies, and genome-wide association studies (GWAS) have not produced any statistically significant results. Our recently initiated genomics study, the Diabetic Retinopathy Genomics (DRGen) Study, aims to examine the contribution of rare and common variants in the development DR, and how they can contribute to clinical phenotype, rate of progression, and response to available therapies. Our preliminary findings reveal a novel set of genetic variants associated with proangiogenic and inflammatory pathways that may contribute to DR pathogenesis. Further investigation of these variants is necessary and may lead to development of novel biomarkers and new therapeutic targets in DR.
Topics: Animals; Biological Variation, Population; Chromosome Mapping; Diabetic Nephropathies; Diabetic Retinopathy; Disease Progression; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genomics; Genotype; Humans; Multifactorial Inheritance; Phenotype; Severity of Illness Index
PubMed: 32295293
DOI: 10.3390/ijms21082712 -
Frontiers in Immunology 2022The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed...
The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed class I molecule with strong associations between disease resistance and MHC haplotype. For Marek's disease virus (MDV) infections of chickens, the MHC haplotype is one of the major determinants of genetic resistance and susceptibility. VALO specific pathogen free (SPF) chickens are widely used in biomedical research and vaccine production. While valuable findings originate from MDV infections of VALO SPF chickens, their MHC haplotypes and associated disease resistance remained elusive. In this study, we used several typing systems to show that VALO SPF chickens possess MHC haplotypes that include B9, B9:02, B15, B19 and B21 at various frequencies. Moreover, we associate the MHC haplotypes to MDV-induced disease and lymphoma formation and found that B15 homozygotes had the lowest tumor incidence while B21 homozygotes had the lowest number of organs with tumors. Finally, we found transmission at variable levels to all contact birds except B15/B21 heterozygotes. These data have immediate implications for the use of VALO SPF chickens and eggs in the life sciences and add another piece to the puzzle of the chicken MHC complex and its role in infections with this oncogenic herpesvirus.
Topics: Animals; Carcinogenesis; Chickens; Disease Resistance; Haplotypes; Herpesvirus 2, Gallid; Histocompatibility Antigens; Major Histocompatibility Complex; Marek Disease
PubMed: 35693787
DOI: 10.3389/fimmu.2022.908305 -
Veterinary World Jan 2023Marek's disease (MD) is a common lymphoproliferative disease affecting chickens and causing economic losses in commercial poultry. The MD outbreak was noticed in the...
BACKGROUND AND AIM
Marek's disease (MD) is a common lymphoproliferative disease affecting chickens and causing economic losses in commercial poultry. The MD outbreak was noticed in the southern part of Thailand in 2019. The suspected cases were found with an abnormal number of cases of layers dying with clinical signs, for example, weakness and emaciation, with evidence of MD gross lesions. This study aimed to raise awareness of the MD outbreak through value chain analysis (VCA), identifying associated possible risk factors, and estimating the associated economic impact.
MATERIALS AND METHODS
Value chain analysis, including seasonal calendar, value chain diagram, and layer movement mapping of the layer industry, was conducted. High-risk stakeholders were identified on the basis of risk practices and interactions between stakeholders. A case-control study was conducted to determine risk factors associated with the MD outbreak on layer farms, and partial budget analysis was used to estimate economic losses associated with MD.
RESULTS
The value chain diagram showed the linkages between stakeholders, including estimation of the percentage of products moved from one stakeholder group to another and the negotiated price. Fourteen out of 35 layer farms were case farms. Farm size and source of birds were significantly associated with the MD outbreak. The MD outbreak caused total economic losses of 295,823 USD. Farms that slaughtered infected birds with additional revenues incurred losses of 140,930 USD, whereas farms that culled infected birds without additional revenue returned incurred losses of 1995 USD.
CONCLUSION
The VCA provided a better understanding of the layer and egg businesses in South Thailand and guided the development of questionnaires for outbreak investigation. The potential risk factor findings suggested the need for further exploration of the source of the MD outbreak.
PubMed: 36855347
DOI: 10.14202/vetworld.2023.35-45 -
Frontiers in Aging Neuroscience 2023To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing...
INTRODUCTION
To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing PD. This is often difficult because most of the clinical markers are non-specific, common in PD but also common in older adults (e.g., sleep problems).
OBJECTIVE
We aimed to identify the clinical markers at high specificity for developing PD by comparing individuals with PD or prodromal PD to healthy controls.
METHODS
We investigated motor and non-motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 1 and 2 items) in 64 prodromal PD and 422 PD individuals calculating the odds ratios, adjusting for age and gender, for PD and prodromal PD versus 195 healthy controls. Symptoms at high specificity were defined as having an adjusted odds ratio ≥ 6.
RESULTS
Constipation had an adjusted odds ratio, 6.14 [95% CI: 2.94-12.80] showing high specificity for prodromal PD, and speech difficulties had an adjusted odds ratio, 9.61 [95% CI: 7.88-48.81] showing high specificity for PD. The proportion of participants showing these specific markers was moderate (e.g., prevalence of constipation was 43.75% in prodromal PD, and speech difficulties was 33.89% in PD), suggesting these symptoms may make robust predictors of prodromal PD and PD, respectively.
DISCUSSION
Clinical markers at high specificity for developing PD could be used as tools in the screening of general populations to identify individuals at higher risk of developing PD.
PubMed: 37810617
DOI: 10.3389/fnagi.2023.1232387 -
Frontiers in Veterinary Science 2024MicroRNAs (miRNAs) serve as key regulators in gene expression and play a crucial role in immune responses, holding a significant promise for diagnosing and managing... (Review)
Review
MicroRNAs (miRNAs) serve as key regulators in gene expression and play a crucial role in immune responses, holding a significant promise for diagnosing and managing diseases in farm animals. This review article summarizes current research on the role of miRNAs in various farm animal diseases and mycotoxicosis, highlighting their potential as biomarkers and using them for mitigation strategies. Through an extensive literature review, we focused on the impact of miRNAs in the pathogenesis of several farm animal diseases, including viral and bacterial infections and mycotoxicosis. They regulate gene expression by inducing mRNA deadenylation, decay, or translational inhibition, significantly impacting cellular processes and protein synthesis. The research revealed specific miRNAs associated with the diseases; for instance, gga-miR-M4 is crucial in Marek's disease, and gga-miR-375 tumor-suppressing function in Avian Leukosis. In swine disease such as Porcine Respiratory and Reproductive Syndrome (PRRS) and swine influenza, miRNAs like miR-155 and miR-21-3p emerged as key regulatory factors. Additionally, our review highlighted the interaction between miRNAs and mycotoxins, suggesting miRNAs can be used as a biomarker for mycotoxin exposure. For example, alterations in miRNA expression, such as the dysregulation observed in response to Aflatoxin B1 (AFB1) in chickens, may indicate potential mechanisms for toxin-induced changes in lipid metabolism leading to liver damage. Our findings highlight miRNAs potential for early disease detection and intervention in farm animal disease management, potentially reducing significant economic losses in agriculture. With only a fraction of miRNAs functionally characterized in farm animals, this review underlines more focused research on specific miRNAs altered in distinct diseases, using advanced technologies like CRISPR-Cas9 screening, single-cell sequencing, and integrated multi-omics approaches. Identifying specific miRNA targets offers a novel pathway for early disease detection and the development of mitigation strategies against mycotoxin exposure in farm animals.
PubMed: 38803799
DOI: 10.3389/fvets.2024.1372961 -
Medical Mycology Oct 2023The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our... (Review)
Review
The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients.
Topics: Humans; Aspergillosis; Hematopoietic Stem Cell Transplantation; Fungi; Mycoses; Environmental Monitoring
PubMed: 37793805
DOI: 10.1093/mmy/myad103 -
Viruses Jul 2023Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested...
Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.
Topics: Animals; Chick Embryo; Hydroxycholesterols; Marek Disease; Chickens; Interferon-alpha; Antiviral Agents; Interferon Type I; Virus Replication
PubMed: 37631994
DOI: 10.3390/v15081652