Telomeric repeats in the commercial SB-1 vaccine facilitate viral integration and contribute to vaccine efficacy

Marek’s disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine viru...

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Bibliographic Details
Published in:npj vaccines 2024-08, Vol.9 (1), p.154-8
Main Authors: You, Yu, Kheimar, Ahmed M., Vychodil, Tereza, Kossak, Lisa, Sabsabi, Mohammad A., Conradie, Andelé M., Reddy, Sanjay M., Bertzbach, Luca D., Kaufer, Benedikt B.
Format: Article
Language:English
Subjects:
631/326/596/1553
631/67/1858
Artificial chromosomes
Biomedical and Life Sciences
Biomedicine
Chickens
Chromosomes
Experiments
Genomes
Herpes viruses
Infectious Diseases
Lymphocytes
Lymphoma
Medical Microbiology
Phosphatase
Polymorphism
Poultry
Public Health
Vaccine
Vaccines
Veterinary medicine
Virology
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Summary:Marek’s disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine virus is commonly used in commercial bivalent vaccines against MDV and also contains TMRs at its ends. Here, we demonstrate that SB-1 efficiently integrates its genome into the chromosomes of latently infected T cells. Deletion of the TMRs from the SB-1 genome did not affect virus replication, but severely impaired virus integration and genome maintenance in latently infected T cells and in chickens. Strikingly, the reduced integration and maintenance of latent SB-1 significantly impaired vaccine protection. Taken together, our data revealed that the TMRs facilitate SB-1 integration and that integration and/or maintenance of the latent viral genome is critical for vaccine protection.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-024-00945-6