Latent infection with Epstein-Barr virus (EBV) is associated with several human cancers, including nasopharyngeal cancer. During latent EBV infections, the glycine-alanine repeat (GAr) domain of the EBV nuclear antigen-1 (EBNA1) inhibits translation of EBNA1 mRNA, thereby suppressing the production of antigenic peptides that the human immune system recognises as foreign. Here, Blondel et al. establish a yeast-based assay that recapitulates GAr-mediated suppression of EBNA1 mRNA translation and use it to identify doxorubicin and its active analogues as compounds that specifically interfere with GAr-mediated suppression of translation. Importantly, in mammalian cells, doxorubicin and its analogues stimulate EBNA1 expression in a GAr-dependent manner and overcome the GAr-dependent restriction of antigen presentation. Together, these results validate the yeast-based assay as an effective cell-based screening approach for compounds that interfere with EBV immune evasion and that might, therefore, provide treatments for EBV-related diseases, including cancer. Page 435
Development/DMM Virtual Meeting 2021
Welcoming new Editors to DMM
Editor-in-Chief Liz Patton wants DMM to strengthen its presence in the field of translational biology and to focus on the importance of disease mechanisms, just as much as models. To implement this vision, we are pleased to welcome new Editors Sally Dunwoodie (Victor Chang Cardiac Research Institute, Australia), Monkol Lek (Yale School of Medicine, USA) and Rickie Patani (Francis Crick Institute, London, UK) to the team.
Roles of the gut microbiome in colorectal cancer development
Going hand-in-hand, a new Perspective by Foegeding et al. explores the Western diet as a driver of dysbiosis in colorectal cancer while a new Review by Wang et al. focuses on microbiota-driven mechanisms that initiate sporadic colorectal cancer.
preLights – the latest disease modelling preprints
Head over to preLights for the digests of the latest preprints:
Erin McGregor highlights work by Nowicka et al. that suggests a potential connection between mitochondrial dysfunction and neurodegeneration.
Emma Wilson discusses work by Dagra et al., which highlights D2 receptors as a potential target that could be used to alleviate alpha-Synuclein pathology in Parkinson’s disease.
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