UL24 deletion attenuates Marek's disease virus replication and pathogenicity

Area of Science:

• Virology
• Immunology
• Oncology

Background:

• Marek's disease virus (MDV) is an oncogenic alphaherpesvirus causing immunosuppression and T-cell lymphomas in chickens.
• The UL24 gene's role in MDV pathogenesis is currently undefined, despite its conservation and importance in other alphaherpesviruses.

Purpose of the Study:

• To investigate the function of the UL24 gene in MDV replication and pathogenesis.
• To assess the potential of UL24 as a target for MDV vaccine development.

Main Methods:

• Construction of a UL24-deletion mutant (Md5BACΔUL24) and revertant using Red-mediated recombination.
• In vitro assessment of viral replication through plaque size and genome copy number.
• In vivo evaluation of virulence in specific pathogen-free (SPF) chickens, including viral load, lymphoid organ assessment, and tumor development.
• Bioinformatic analysis of the MDV UL24 protein sequence.

Main Results:

• UL24 deletion significantly impaired in vitro viral replication, showing smaller plaques and reduced viral genome copies.
• In chickens, UL24 deficiency markedly decreased viral loads, prevented lymphoid organ atrophy, and abolished tumor formation.
• Bioinformatic analysis identified a nuclear localization signal and an endonuclease motif in MDV UL24, suggesting nuclear functions.

Conclusions:

• The UL24 gene plays a critical role in MDV replication and pathogenesis.
• UL24 is a promising target for developing attenuated MDV vaccines or recombinant vaccine vectors.