Telomeres protect the ends of vertebrate chromosomes from deterioration and consist of tandem nucleotide repeats (TTAGGG)n that are associated with a number of proteins. Shortening of the telomeres occurs during genome replication, thereby limiting the replication potential of somatic cells. To counteract this shortening, vertebrates encode the telomerase complex that maintains telomere length in certain cell types via de novo addition of telomeric repeats. Several herpesviruses, including the highly oncogenic alphaherpesvirus Marek’s disease virus (MDV), harbor telomeric repeats (TMR) identical to the host telomere sequences at the ends of their linear genomes. These TMR facilitate the integration of the MDV genome into host telomeres during latency, allowing the virus to persist in the host for life. Integration into host telomeres is critical for disease and tumor induction by MDV, but also enables efficient reactivation of the integrated virus genome. In addition to the TMR, MDV also encodes a telomerase RNA subunit (vTR) that shares 88% sequence identity with the telomerase RNA in chicken (chTR). vTR is highly expressed during all stages of the virus lifecycle, enhances telomerase activity and plays an important role in MDV-induced tumor formation. This review will focus on the recent advances in understanding the role of viral TMR and vTR in MDV pathogenesis, integration and tumorigenesis.
Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes a devastating neoplastic disease in chickens. MDV has been shown to integrate its genome into the telomeres of latently infected and tumor cells, which is crucial for efficient tumor formation. Telomeric repeat arrays present at the ends of the MDV genome facilitate this integration into host telomeres; however, the integration mechanism remains poorly understood. Until now, MDV integration could only be investigated qualitatively upon infection of chickens. To shed further light on the integration mechanism, we established a quantitative integration assay using chicken T cell lines, the target cells for MDV latency and transformation. We optimized the infection conditions and assessed the establishment of latency in these T cells. The MDV genome was efficiently maintained over time, and integration was confirmed in these cells by fluorescence in situ hybridization (FISH). To assess the role of the two distinct viral telomeric repeat arrays in the integration process, we tested various knockout mutants in our in vitro integration assay. Efficient genome maintenance and integration was thereby dependent on the presence of the telomeric repeat arrays in the virus genome. Taken together, we developed and validated a novel in vitro integration assay that will shed light on the integration mechanism of this highly oncogenic virus into host telomeres.
Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and integrates its genome into the telomeres of latently infected cells. MDV encodes two proteins, UL12 and UL29 (ICP8), that are conserved among herpesviruses and could facilitate virus integration. The orthologues of UL12 and UL29 in herpes simplex virus 1 (HSV-1) possess exonuclease and single strand DNA-binding activity, respectively, and facilitate DNA recombination; however, the role of both proteins in the MDV lifecycle remains elusive. To determine if UL12 and/or UL29 are involved in virus replication, we abrogated their expression in the very virulent RB-1B strain. Abrogation of either UL12 or UL29 resulted in a severe impairment of virus replication. We also demonstrated that MDV UL12 can aid in single strand annealing DNA repair, using a well-established reporter cell line. Finally, we assessed the role of UL12 and UL29 in MDV integration and maintenance of the latent virus genome. We could demonstrate that knockdown of UL12 and UL29 does not interfere with the establishment or maintenance of latency. Our data therefore shed light on the role of MDV UL12 and UL29 in MDV replication, DNA repair, and maintenance of the latent virus genome.
Faecal microbiota transplantation (FMT) has emerged as a transformative therapy in human medicine, particularly for managing recurrent Clostridioides difficile infections and other gastrointestinal (GI) disorders. Beyond the GI tract, FMT has shown potential in addressing extraintestinal conditions in people, including metabolic, immune-mediated, dermatological, neurological, and infectious diseases. Research in people has highlighted its efficacy in decolonising multidrug-resistant organisms in infection, mitigating autoimmune diseases, and improving outcomes in metabolic disorders such as obesity and diabetes. Furthermore, FMT has also been linked to enhanced responses to immunotherapy in cancer and improved management of hepatic and renal conditions. These findings underscore the intricate connections between the gut microbiome and systemic health, opening novel therapeutic avenues. In veterinary medicine, while FMT has demonstrated benefits for GI disorders, its application in extraintestinal diseases remains largely unexplored. Emerging evidence suggests that conditions such as atopic dermatitis, chronic kidney disease, immune-mediated diseases, and behavioural disorders in companion animals could benefit from microbiome-targeted therapies. However, significant gaps in knowledge persist, particularly regarding the long-term safety and efficacy for veterinary applications. This review synthesises findings from human medicine to assess their relevance for veterinary applications and future research.
Educating clients and teaching and mentoring colleagues are crucial yet underappreciated elements of a veterinarian's professional duties. Unfortunately, veterinary curricula rarely explicitly aim to encourage students to develop effective teaching practices. This study describes a novel 1‐ to 2‐week immersive anatomy education extramural studies (EMS) placement, designed to allow fourth‐ and fifth‐year veterinary medicine students to experience teaching within a professional environment. This study aimed to evaluate the experiences of undergraduate veterinary medicine students and support staff engaged in this opportunity, with a view to exploring the holistic benefits of an anatomy education professional work placement. During 2023–24, 8 students and 4 members of support staff took part in semi‐structured online interviews to explore their placement experiences. Thematic analysis using a grounded theory approach resulted in four themes: Quality Learning, Professional Development, A Safe Space for Personal Development, and The Vet as Teacher. Students were engaged in self‐directed, active and experiential learning, reported enhanced intrinsic motivation for learning, and improved appreciation of the clinical relevance of anatomy. Students developed professional skills, including multiple aspects of communication, and enhanced awareness of diversity. The placement allowed students to develop personal attributes such as self‐efficacy, intellectual humility and uncertainty tolerance in a supportive, safe space. Students strongly identified with the role of a veterinarian as an educator. Consideration should be given to creating formal supported opportunities for students to be actively involved in educating others to enhance student awareness of this crucial professional responsibility and support the development of those necessary skills.
Social network analysis (SNA) is an increasingly utilised technique in the literature examining the social structures and organisation of animals and understanding the bonds between groups and individuals. Using a case study as an illustration, the applications of SNA are explored, including the identification of dominance hierarchies and detection of sources of social pressure, with a particular focus on the applications of SNA to holistic assessments of animal welfare alongside other methods. Based on the examination of social dynamics in a family group of four black lemurs (Eulemur macaco), a primate whose social organisation is characterised by patterns of female dominance, it is demonstrated that SNA can be used to examine the affiliative and agonistic interactions between individuals living in human care. SNA showed species-typical forms of female dominance that were largely directed towards the two males, characterised by the initiation of aggressive interactions and male submission. More intricate relationships and consistent social roles across networks were revealed through the examination of SNA. It is concluded that SNA has wide-ranging benefits in the assessment of effects of environmental changes, such as informing social management decisions, developing enrichment and intervention programs, and guiding overall improvements to the housing and care of individual animals. SNA, as part of an animal welfare toolbox, could, therefore, be a pivotal technique for modern animal welfare assessment that considers individual animals and their social lives. By sharing a case study of the technique in use, it is hoped that animal collections may adopt similar modern and evidence-based assessment methods.