Search Results (127)

Herpesvirus infections, including herpes simplex virus (HSV), Epstein–Barr virus (EBV), and cytomegalovirus (CMV), present significant challenges in diagnosis, treatment, and transmission control. Despite advances in medical technology, managing these infections remains complex due to the viruses’ ability to establish latency and their widespread prevalence. Artificial Intelligence (AI) has emerged as a transformative tool in biomedical science, enhancing our ability to understand, predict, and manage infectious diseases. In veterinary virology, AI applications offer considerable potential for improving diagnostics, forecasting outbreaks, and implementing targeted control strategies. This review explores the growing role of AI in advancing our understanding of herpesvirus infection, particularly those caused by MDV, through improved detection, transmission modeling, treatment strategies, and predictive tools. Employing AI technologies such as machine learning (ML), deep learning (DL), and natural language processing (NLP), researchers have made significant progress in addressing diagnostic limitations, modeling transmission dynamics, and identifying potential therapeutics. Furthermore, AI holds the potential to revolutionize personalized medicine, predictive analytics, and vaccine development for herpesvirus-related diseases. The review concludes by discussing ethical considerations, implementation challenges, and future research directions necessary to fully integrate AI into clinical and veterinary practice. Full article

Marek’s disease (MD), induced by the highly contagious Marek’s disease virus (MDV), remains a significant challenge to global poultry health despite extensive vaccination efforts. This study employed integrated transcriptomic and metabolomic analyses to investigate liver responses in naturally MDV-infected Wenchang chickens during late infection stages. RNA sequencing identified 959 differentially expressed genes (DEGs) between the infected and uninfected groups. Functional enrichment analysis demonstrated that these DEGs were primarily associated with canonical pathways related to metabolism and cellular processes, including lipid, carbohydrate, and amino acid metabolism, as well as the p53 signaling pathway, cell cycle, and apoptosis. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) detected 561 differentially expressed metabolites (DEMs), showing near-significant enrichment (p = 0.069) in phenylalanine metabolism. Integrated analysis of transcriptomics and metabolomics data highlighted that critical gene–metabolite pairs such as SGPL1-palmitaldehyde–sphinganine-1-phosphate and ME1-NADP+–malic acid potentially mediate functional crosstalk between sphingolipid metabolism and cellular redox homeostasis during viral oncogenesis. This comprehensive mapping of regulatory networks provides insights into host–virus interactions during MDV pathogenesis, offering potential applications in immunomodulation approaches, targeted therapeutic strategies, and vaccine adjuvant development. Full article

Marek’s Disease Virus (MDV) is a highly contagious pathogen in chickens, resulting in immunosuppression and T-cell lymphomas. Understanding the role of host cytokines in MDV pathogenesis is crucial for developing effective interventions. This study investigated the in vivo effects of overexpressing avian interleukin-17 (IL-17) in Marek’s disease virus infection model and its impact on T-cell populations. We utilized a recombinant pCDNA3.1 plasmid that expresses IL-17 at days 4 and 10 post-MDV infection in chickens. Our findings demonstrate that IL-17 overexpression significantly enhanced MDV replication. However, treatment with the plasmid expressing IL-17 led to a reduction in MD disease severity. Additionally, IL-17 treatment markedly altered the frequency of CD4+ and CD8α+ αβ T-cells. Specifically, at 21-dpi, there was an increase in CD3+ CD8α+ αβ T cells and a decrease in CD3+ CD4+ αβ T-cells within the spleen of chickens treated with the plasmid expressing IL-17. These modulatory effects suggest a possible mechanism by which IL-17 facilitates immune system cell activation and enhances viral persistence. This study underscores the pivotal role of IL-17 in MDV infection dynamics and offers. Full article

Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect chickens against additional unrelated pathogens. Because HVT replicates in a strictly cell-associated fashion to low levels of infectious units, adherent primary chicken or duck embryo fibroblasts are infected, dislodged from the cultivation surface and distributed as cryocultures in liquid nitrogen to the site of application. Although viable cells are complex products, application of infected cells in ovo confers protection even in presence of maternal antibodies. Methods/Results: The aim of our study was to determine whether a continuous cell line in a scalable cultivation format can be used for production of HVT-based vaccines. The AGE1.CR cell line (from Muscovy duck) was found to be highly permissive in adherent cultures. Propagation in suspension, however, initially gave very low yields. The induction of cell-to-cell contacts in carrier-independent suspensions and a metabolic shock improved titers to levels suitable for vaccine production (>10⁵ infectious units/mL after infection with multiplicity of 0.001). Conclusions: Production of HVT is challenging to scale to large volumes and the reliance on embryonated eggs from biosecure facilities is complex. We demonstrate that a cell-associated HVT vector can be propagated in a carrier-independent suspension culture of AGE1.CR cells in chemically defined medium. The fed-batch production is independent of primary cells and animal-derived material and can be scaled to large volumes. Full article

Marek’s disease virus (MDV) is the etiological agent of Marek’s disease (MD), a lymphoproliferative disorder in chickens. Polymorphisms in the MDV-encoded oncoprotein Meq are shared among field strains and correlate with their virulence. The attenuated vaccine strain CVI988 harbors unique amino acid polymorphisms in Meq, particularly at positions 71, 77, and 326. In this study, we investigated the impact of these polymorphisms on Meq protein function and MDV virulence. Reporter assays revealed that the substitutions, particularly A71S and K77E, markedly impaired the transcriptional regulatory activity of Meq. To evaluate their effect on virulence, we generated a recombinant MDV based on the very virulent RB-1B strain, encoding Meq with A71S and K77E substitutions (rRB-1B_Meq71/77). Chickens infected with rRB-1B_Meq71/77 developed neither clinical signs nor lymphomas. Flow cytometry revealed no expansion of infected cells in this group, but a marked increase in CD8⁺ T and γδ T cells during early infection. Histopathological analysis also confirmed the absence of MD-associated lesions. These findings demonstrate that the polymorphisms at positions 71 and 77 in the CVI988 strain are sufficient to abolish MDV virulence. This study provides insight into the molecular basis of MDV virulence and informs the strategy for the design of more effective vaccines. Full article

Mortality from Marek’s disease virus (MDV) infection results in economic loss for the poultry industry. It is controlled by vaccination, but the virus mutates and becomes more virulent. Variation within the MHC is well known to impact the outcomes following MDV infection from research performed utilizing the White Leghorn breed, with laboratory strains of the virus. The effect of the MHC haplotype following MDV challenge was determined from six lines of commercial elite (White Plymouth Rock (two), White Leghorn (three), and Rhode Island Red (one)) egg layer lines, challenged with vv+ virus. Mortality was recorded as sire daughter averages at 16–18 weeks of age from 19 generations of data. Sires were genotyped using a set of MHC-specific SNPs, encompassing 210,000 bp. Across all lines, there was a total of 23 unique MHC haplotypes, of which 15 were found at a frequency greater than 5% and used for further analysis. A significant impact on mortality was found for 16 of the haplotypes, with 9 haplotypes associated with decreased mortality and 7 haplotypes with increased mortality. There were three haplotypes identified in more than one line, allowing cross-line comparisons. The effect of these common haplotypes was consistent (either negative, positive or neutral) between lines. Full article

The glycoprotein C (gC) of gallid alphaherpesvirus 2—better known as Marek’s disease (MD) virus (MDV)—and gallid alphaherpesvirus 3 is required for horizontal transmission in chickens. Since gC is conserved within the Alphaherpesvirinae subfamily, we hypothesized that gC was also essential for the horizontal transmission of meleagrid alphaherpesvirus 1 (MeAHV1) or turkey herpesvirus (HVT). To test this hypothesis, we generated a fluorescent protein-tagged clone of recombinant (r)HVT (vHVT47G), removed the open reading frame of HVT gC from the genome (vHΔgC), and rescued the deletion by inserting an HA-epitope tagged HVT gC (vHΔgC-R) to test their ability to transmit in chickens and turkeys. We also tested whether MDV gC could compensate for HVT gC during transmission, where HVT gC was replaced with MDV gC (vH-MDVgC). Although all viruses replicated in chickens, none spread from chicken to chicken. However, when tested in turkeys, all viruses except vHΔgC transmitted from turkey to turkey. Importantly, the rescuent virus (vHΔgC-R) and HVT expressing MDV gC (vH-MDVgC) rescued transmission, showing that HVT gC is required and MDV gC can compensate for HVT gC for turkey-to-turkey transmission. These data confirm the host-specific transmission of HVT in turkeys and suggest that the essential function of alphaherpesvirus gC proteins is conserved. This information can be exploited while generating future vaccines against MD that will affect the poultry industry worldwide. Full article

The poultry farming industry encounters considerable obstacles stemming from viral diseases, resulting in elevated mortality rates and substantial economic losses. Current research highlights the significant involvement of long non-coding RNAs (lncRNAs) in the interactions between hosts and pathogens by enhancing antiviral responses at different levels, such as the activation of pathogen recognition receptors, as well as through epigenetic, transcriptional, and post-transcriptional modifications. Specific long non-coding RNAs (lncRNAs), including ERL lncRNA, linc-GALMD3, and loc107051710, have been recognized as significant contributors to the antiviral immune response to multiple avian viral pathogens. Understanding the mechanisms by which long non-coding RNAs (lncRNAs) act offers valuable insights into prospective diagnostic and therapeutic approaches aimed at improving disease resistance in poultry. Differentially expressed lncRNAs may also be utilized as biomarkers for both prognosis and diagnosis of avian viral diseases. This review delves into the various roles of long non-coding RNAs (lncRNAs) in the context of viral diseases in chickens, such as avian leukosis, Marek’s disease, infectious bursal disease, avian influenza, infectious bronchitis, and Newcastle disease. It highlights the pivotal role of lncRNAs in the complex dynamics between the host and viral pathogens, particularly their interactions with specific viral proteins. Understanding these interactions may provide valuable insights into the spatial and temporal regulation of lncRNAs, aid in the identification of potential drug targets, and reveal the expression patterns of lncRNA and coding gene transcripts in response to different viral infections in avian species. Full article

Marek’s disease (MD) is a highly contagious and oncogenic viral disease of poultry, causing significant economic losses due to mortality and reduced performance. The rapid evolution of Marek’s disease virus (MDV) has been reported in poultry farms, often overcoming vaccination and leading to disease outbreaks. This study aimed to detect and molecularly characterize circulating MDV strains in Tanzania, with a focus on their genetic relationship with the vaccine strains currently in use (HVT and CVI988). Samples were collected from six livestock representative zones in Tanzania (Central, Eastern, Southern, Southern Highlands, Lake, and Northern Zone) and analyzed using polymerase chain reaction (PCR) and sequencing of key oncogenic genes (meq, pp38, and vIL-8). Phylogenetic analysis was conducted using MEGA 12 software to determine the genetic relationships between Tanzanian isolates and MDV strains from Africa and other continents. The results confirm the widespread circulation of MDV in Tanzania, with an overall prevalence of 18.08% across all surveyed zones. Molecular characterization of the meq, pp38, and vIL-8 genes revealed high sequence similarity with previously reported MDV strains from Egypt, Nigeria, Israel, and China, with clustering observed in the phylogenetic analysis. Notably, Tanzanian MDV strains exhibited amino acid substitutions associated with increased virulence, particularly in the meq gene, which plays a crucial role in MDV-induced tumorigenesis. These findings suggest that MDV strains in Tanzania have undergone genetic changes that could potentially affect vaccine efficacy. Therefore, this study provides valuable information for vaccine manufacturers, poultry farmers, and policymakers in Tanzania, enabling informed decisions when selecting vaccines for MD control. Full article

This retrospective study investigated the clinical presentation, diagnostic findings, and treatment outcomes in 419 backyard (pet) chickens admitted to the Service for Avian and Reptiles at the University of Veterinary Medicine Vienna from 1 May 2009 to 30 April 2019. The median age of the chickens was 1.5 years, with 83.8% being female. The majority (80.0%) presented with individual clinical issues, while 20.0% were diagnosed with flock diseases. The most common admission causes included unspecific clinical signs (57.3%), respiratory tract issues (18.4%), and locomotor problems (16.2%). Diagnostic imaging modalities such as ultrasonography, radiography, and CT scans revealed pathologies, including ascites, salpingitis, and skeletal system abnormalities. Parasitological examinations found a high rate of coccidia, Capillaria, and Ascaridia, while microbiological analysis identified Escherichia coli and Pasteurella multocida as common bacterial pathogens. The most prevalent diseases were upper respiratory tract infections (13.8%), egg peritonitis (9.9%), and soft tissue trauma (9.4%). Treatment outcomes showed that 67.5% survived to discharge, while 32.2% died or were euthanized. Surgical interventions were performed in 25.3% of cases, with the most common surgeries being salpingohysterectomy and wound debridement. This study highlights the wide range of health issues faced by pet chickens and emphasizes the importance of accurate diagnosis and targeted treatment in avian veterinary care. It also underscores the role of various diagnostic tools, such as imaging, pathogen detection, and histopathology, in addressing the health challenges of backyard chickens. Full article

Marek’s disease virus (MDV) causes Marek’s disease (MD) in chickens, characterized by malignant lymphomas and immunosuppression. Sporadic MD outbreaks continue to occur even among vaccinated flocks in certain regions due to the increased virulence of the field strains. However, the mechanisms of tumorigenesis and immunosuppression caused by MDV remain to be fully elucidated. We previously reported that the mRNA expression of programmed cell death 1 (PD-1), an immune checkpoint molecule, was increased in tumor lesions caused by MDV, and its expression was positively correlated with the mRNA expression of Meq, an MDV-specific oncogene. In this study, we characterized PD-1-expressing T-cell subsets in the spleen and tissues of chickens that developed tumors to investigate the association between PD-1 expression and immunosuppression. Flow cytometric analysis revealed that the proportion of PD-1-expressing CD4⁺ T-cells, which are targets of MDV tumorigenesis, increased in the spleen and tumor tissues of chickens with MD. The proportion of PD-1⁺ CD4⁺ T-cells was higher in Meq-expressing cells than in those that were not. In the spleens of chickens with MD, the proportions of PD-1-expressing cells were increased in CD8⁺ and γδ T-cells, which play pivotal roles in defense against MD pathogenesis, relative to those of spleens from uninfected chickens. Moreover, the proportion of PD-1⁺ CD8⁺ T-cells expressing interferon (IFN)-γ did not increase in the spleen of chickens with MD. Additionally, no difference in the proportion of IFN-γ⁺ γδ T-cells expressing and not expressing PD-1 was observed in the spleens of chickens with MD, although the proportion of IFN-γ⁺ γδ T-cells expressing PD-1 in the spleens of uninfected chickens was higher. The function of PD-1-expressing CD8⁺ and γδ T-cells in chickens may be impaired after developing MD, which may cause MDV-induced immunosuppression. Full article

There are about 5000 species of Passeriformes birds, which are half of the extant ones. Their class I MHC molecules are found to be different from all other studied vertebrates, including other bird species; i.e., amino acid residues 10 and 96 are not the seven canonic residues extant in all other vertebrate molecules. Thus, the canonic residues in MHC class I vertebrate molecules are reduced to five. These differences have physical effects in MHC (Major Histocompatibility Complex) class I alpha chain interaction with beta-2-microglobulin but have yet unknown functional effects. Also, introns show specific Passeriformes distinction both in size and invariance. The studies reviewed in this paper on MHC structure have been done in wild birds that cover most of the world’s passerine habitats. In this context, we are going to expose the most commonly occurring bird diseases with the caveat that MHC and disease linkage pathogenesis is not resolved. In addition, this field is poorly studied in birds; however, common bird diseases like malaria and Marek’s disease are linked to MHC. On the other hand, the main established function of MHC molecules is presenting microbial and other antigens to T cells in order to start immune responses, and they also may modulate the immune system through NK receptors and other receptors (non-classical class I MHC molecules). Also, structural and polymorphic differences between classical class I molecules and non-classical class I molecules are at present not clear, and their definition is blurred. These passerine exceptional MHC class I molecules may influence linkage to diseases, transplantation, and other MHC presentation and self-protection functions. Further studies in more Passeriformes species are ongoing and needed. Full article

The gallid alphaherpesvirus 3 (GaAHV3) SB-1, a Mardivirus used as a vaccine against Marek’s disease, has been proposed as an interesting viral vector for poultry vaccination. However, SB-1 is highly transmissible between chickens, a feature that may be a limitation for the use of live recombinant vaccines. We have previously shown that UL47 is essential for horizontal transmission of the pathogenic Marek’s disease virus between chickens, but it is completely dispensable for replication and pathogenesis. In contrast, the role of UL47 in the biology of SB-1 remains unknown. To study that, we generated an SB-1 mutant lacking UL47 (∆47) from a commercial SB-1 isolate. This mutant replicated and spread like the WT in primary fibroblasts, indicating no growth defects in cell culture. In vivo, chickens inoculated with ∆47 had significantly reduced viral loads in the blood and the spleen, and transport to the skin was delayed compared to WT inoculated chickens. Strikingly, the ∆47 mutant was present in 66% of contact birds. As expected, 100% of contact birds were positive for the WT. In conclusion, our findings reveal that UL47 facilitates GaAHV3 SB-1 replication in vivo, which is important for latency establishment but is not essential for horizontal transmission, unlike for MDV. Full article

Marek’s disease (MD), characterized by the rapid onset of T-cell lymphomas in chickens, is caused by Mardivirus gallidalpha2, an oncogenic alphaherpesvirus commonly known as Marek’s disease virus (MDV). MDV encodes a bZIP protein, Meq, which contains a bZIP domain (basic DNA-binding and leucine zipper dimerization domain) at the amino terminus and a transcriptional regulatory domain at the carboxyl end. Meq can transform murine and chicken fibroblasts in vitro and is essential for tumor formation in chickens. Meq homodimerization and heterodimerization through its bZIP domain are involved in Meq-mediated transformation. However, the role of Meq DNA-binding and transcriptional regulatory domains in transformation has not been investigated. In this study, we constructed recombinant Md5 (very virulent MDV) viruses expressing chimeric Meq proteins generated by swapping the DNA-binding and transcriptional regulatory domains of Meq of Md5 and vaccine (CVI988/Rispens) strains. Our results show that these recombinant viruses, rMd5-Md5/CVI-Meq (Md5 DNA-binding domain and CVI transcriptional regulatory domain) and rMd5-CVI/Md5-Meq (CVI DNA-binding domain and Md5 transcriptional regulatory domain), replicated at levels similar to parental rMd5 in cell culture and chickens and could transmit efficiently among chickens. Interestingly, parental rMd5 and chimeric viruses exhibited distinct pathogenic phenotypes in chickens: rMd5 caused 100% mortality, a moderate level of tumor incidence in visceral organs and small visceral tumors; rMd5-Md5/CVI-Meq caused 100% mortality, a high level of tumor incidence in visceral organs, and very large visceral tumors; while rMd5-CVI/Md5-Meq caused an average of 37% mortality, rarely induced tumors in visceral organs, and the visceral tumors were small. In conclusion, our study suggests that the DNA-binding domain of Meq plays an essential role in transformation (tumor incidence), while the transcriptional regulatory domain of Meq influences the distribution and size of MDV-induced tumors. Full article

Very virulent plus Marek’s disease virus (vv+MDV) induces severe immunosuppression in commercial chickens. In this study, we evaluated how three Gallid alphaherpesvirus 2 (GaHV-2) vaccines (CVI-988, rMd5-BAC∆Meq, and CVI-LTR) protected against two negative outcomes of vv+MDV infection: (1) reduced viability and frequency of immune cells in the spleen and (2) decreased efficacy of the CEO (chicken embryo origin) vaccine against infectious laryngotracheitis challenge. At 25 days post-infection with vv+MDV 686, all vaccines are protected against the reduced viability of splenocytes. However, there were differences in the frequency of splenic immunophenotypes among groups. Compared to the uninfected control, the frequency of B cells was reduced in the CVI-988/686 group but not in the rMd5-BAC∆Meq/686 and CVI-LTR/686 groups. T cell subset frequencies showed no difference between the negative controls and CVI-988/686; however, there was a reduction in activated CD4+ T cells in the rMd5-BAC∆Meq/686 group and in activated CD4+, activated CD8+, and γδ+ T cells in the CVI-LTR/686 group. We also demonstrated that the three vaccines protected against MDV-induced tumors, but only rMd5-BAC∆Meq and CVI-LTR protected against the negative impact of vv+MDV 648A strain on CEO vaccine efficacy. Our findings demonstrate important differences in the biology and/or mechanisms of protection of these vaccines. Full article