Immune escape of avian oncogenic Marek’s disease herpesvirus and antagonistic host immune responses

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 15, 2024

Marek's disease virus (MDV) is a highly pathogenic and oncogenic alpha herpesvirus that causes (MD), which one of the most important immunosuppressive rapid-onset neoplastic diseases in poultry. The onset MD lymphomas other clinical can be efficiently prevented by vaccination; these vaccines are heralded as first demonstration successful vaccination strategy against cancer. However, persistent evolution epidemic MDV strains towards greater virulence has recently resulted frequent outbreaks vaccinated chicken flocks worldwide. Herein, we provide an overall review focusing on discovery identification strategies evades host immunity attacks immune system. We have also highlighted decrease efficacy current vaccines. prospects, new techniques for development efficient vaccines, together with possibilities antiviral therapy MD, discussed.

Language: Английский

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Protection Conferred by Gallid Alphaherpesvirus 2 Vaccines Against Immunosuppression Induced by Very Virulent Plus (vv+) Marek’s Disease Virus Strains in Commercial Meat Type Chickens

Pathogens, Journal Year: 2025, Volume and Issue: 14(1), P. 54 - 54

Published: Jan. 10, 2025

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 frequency immune cells the spleen (2) decreased efficacy CEO (chicken embryo origin) vaccine infectious laryngotracheitis challenge. At 25 days post-infection with 686, all are splenocytes. However, there were differences splenic immunophenotypes among groups. Compared to uninfected control, B was CVI-988/686 group but not rMd5-BAC∆Meq/686 CVI-LTR/686 T cell subset frequencies showed no difference between controls CVI-988/686; however, a reduction activated CD4+ CD4+, CD8+, γδ+ group. We also demonstrated that MDV-induced tumors, only rMd5-BAC∆Meq CVI-LTR impact 648A strain on efficacy. Our findings demonstrate important biology and/or mechanisms protection these vaccines.

Language: Английский

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Programmed Cell Death-1 Expression in T-Cell Subsets in Chickens Infected with Marek’s Disease Virus

Pathogens, Journal Year: 2025, Volume and Issue: 14(5), P. 431 - 431

Published: April 29, 2025

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

Language: Английский

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Chicken γδ T cells proliferate upon IL-2 and IL-12 treatment and show a restricted receptor repertoire in cell culture

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 13, 2024

In chickens, γδ T cells represent a large fraction of peripheral cells; however, their function remains largely unknown. Here, we describe the selective in vitro expansion from total splenocytes by stimulation with cytokines IL-2 and IL-12. Under these conditions, proliferated preferentially reached frequencies >95% within three weeks. Although alone also triggered proliferation, an increased proliferation rate was observed combination Most expanded were TCR CD8 double-positive. Splenocytes sorted into TCR1 + , high − low subsets well upon dual IL-2/IL-12, indicating that none cell require bystander activation for proliferation. maintained surface expression during stimulation, whereas subpopulations showed varied levels upregulation, highest upregulation subset. Changes T-cell receptor repertoire culture day 0 to 21 analyzed next-generation sequencing variable regions. Overall, long-term led restricted γ δ chain repertoire, characterized reduced number unique region clonotypes, specific V genes enriched at 21. On 0, highly diverse, predominant clonotypes differed between animals, while most frequent γ-chain shared animals. However, on 21, both repertoires different dominant seems be individual outcome. conclusion, IL-12 sufficient stimulate outgrowth cells. Analyses indicate leads clones, which may reflect previous vivo activation. This system will instrumental studying function.

Language: Английский

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Preventing bacterial disease in poultry in the post-antibiotic era: a case for innate immunity modulation as an alternative to antibiotic use

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 3, 2023

The widespread use of antibiotics in the poultry industry has led to emergence antibiotic-resistant bacteria, which pose a significant health risk humans and animals. These public concerns, have legislation limiting antibiotic animals, drive need find alternative strategies for controlling treating bacterial infections. Modulation avian innate immune system using immunostimulatory compounds provides promising solution enhance responses broad range infections without generating resistance. An array immunomodulatory been investigated their impact on performance responses. However, further research is required identify capable detrimentally affecting bird performance. It also crucial determine safety effectiveness these conjunction with vaccines. This review an overview various modulators known immunity against pathogens chickens, describes mechanisms involved.

Language: Английский

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Unraveling the role of γδ T cells in the pathogenesis of an oncogenic avian herpesvirus

mBio, Journal Year: 2024, Volume and Issue: 15(8)

Published: July 2, 2024

ABSTRACT Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that causes deadly lymphomas in chickens. In chickens, up to 50% of all peripheral T cells are gamma delta (γδ) cells. Until now, their role MDV pathogenesis and tumor formation remains poorly understood. To investigate the γδ pathogenesis, we infected recently generated cell knockout chickens with very virulent MDV. Strikingly, incidence were highly increased absence cells, indicating play important immune response against replication was drastically thymus spleen, which potential sites transformation. Taken together, our data provide first evidence this herpesvirus. IMPORTANCE Gamma most abundant but fighting pathogens veterinary pathogen, one frequent cancers animals used as a model for virus-induced formation. Our study revealed crucial combating MDV, these restricted key lymphoid organs, thereby decreasing likelihood causing tumors disease. This provides novel insights into virus.

Language: Английский

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Temporal Changes in Splenic Immune Cell Populations following Infection with a Very Virulent plus MDV in Commercial Meat-Type Chickens

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1092 - 1092

Published: July 6, 2024

Marek’s disease virus (MDV) can cause severe immunosuppression in chickens. Our previous study showed that infection with very virulent plus (vv+) MDV strains of one-day-old commercial meat-type chickens possessing maternal antibodies against resulted depletion splenocytes at 28–30 days age. In the present study, we have investigated effect vv+MDV strain 686 on splenic immunophenotypes 6, 20, and 30 post-infection (dpi). Both live dead cells were analyzed, data statistically compared to uninfected control. The results revealed a decrease total cell population starting day primarily affecting B cells, CD8β+, gamma delta (γδ) T while frequencies both CD3+ CD4+ increased. MHC-I expression was higher 20 dpi, MHC-II these downregulated 6 dpi but upregulated dpi. Collectively, suggest seem delay negative effects lymphoid populations, albeit being non-protective. emphasize importance MD vaccination endemic areas.

Language: Английский

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Dynamic alterations in T-lymphocyte subsets assessed by flow cytometry in chickens following exposure to infectious bursal disease virus: a systematic review

Developmental & Comparative Immunology, Journal Year: 2024, Volume and Issue: 162, P. 105280 - 105280

Published: Oct. 11, 2024

Language: Английский

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Role of T Cells in Vaccine-Mediated Immunity against Marek’s Disease

Viruses, Journal Year: 2023, Volume and Issue: 15(3), P. 648 - 648

Published: Feb. 28, 2023

Marek’s disease virus (MDV), a highly cell-associated oncogenic α-herpesvirus, is the etiological agent of T cell lymphomas and neuropathic in chickens known as (MD). Clinical signs MD include neurological disorders, immunosuppression, lymphoproliferative viscera, peripheral nerves, skin. Although vaccination has greatly reduced economic losses from MD, molecular mechanism vaccine-induced protection largely unknown. To shed light on possible role cells immunity induced by vaccination, we vaccinated birds after depletion circulating through IP/IV injection anti-chicken CD4 CD8 monoclonal antibodies, challenged them post-vaccination recovery populations post-treatment. There were no clinical or tumor development vaccinated/challenged with depleted CD4+ CD8+ cells. The combined cells, however, severely emaciated, atrophied spleens bursas. These also tumor-free at termination, particles detected collected tissues. Our data indicated that lymphocytes did not play critical vaccine-mediated against MDV-induced development.

Language: Английский

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Effect of Dietary Chlorella vulgaris or Tetradesmus obliquus on Laying Performance and Intestinal Immune Cell Parameters

Animals, Journal Year: 2023, Volume and Issue: 13(10), P. 1589 - 1589

Published: May 9, 2023

A feeding trial was conducted to investigate the effect of dietary supplementation Chlorella vulgaris (CV) or Tetradesmus obliquus (TO) on laying performance, egg quality, and gut health indicators hens. total 144 Hy-Line Brown hens aged 21 weeks were randomly assigned one three treatments with eight replicates six Dietary as follows: CON, basal diet; CV, diet + 5 g C. vulgaris/kg TO, T. obliquus/kg diet. The results showed that diets supplemented CV TO had insignificant effects quality (i.e., Haugh unit eggshell strength thickness), jejunal histology, cecal short-chain fatty acids, antioxidant/immune markers in ileal mucosa samples Compared control group, yolk color score higher (p < 0.05) fed containing although former a more intense yellow than latter. Small intestinal lamina propria cells isolated using flow cytometry examine percentages immune cell subpopulations. microalgae did not affect B monocytes/macrophages but altered percentage CD4+ T CD8− TCR γδ cells. Collectively, can improve would modulate host development competence

Language: Английский

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