Journal des maladies infectieuses et de la thérapie

Abstrait

Dynamics of Higher-Order Chromatin Structure in Response to Viral Infection and its Potential for Treatment of Infectious Diseases

Yumiko Imai

Viruses hijack cellular functions, primarily including the transcription machinery, through epigenetic mechanisms such as chromatin dynamics and Histone Post-Translational Modifications (HPTM). The spatial organization of chromatin is known to be highly dynamic in response to environmental stresses. In this review, we focus on our recent work demonstrating the dynamics of higher-order chromatin organization in response to influenza virus infection. We focused on the H4K20 trimethyltransferase Suv4-20h2, which interacts with cohesin in the uninfected condition. Upon viral infection, Suv4-20h2 binds to the viral protein and supresses its binding to cohesin. As a result, cohesin is loaded into a specific genomic region and a chromatin loop is formed in that region, resulting in gene expression that promotes viral replication. Inhibiting the binding of viral proteins to Suv4-20h2 is a potential therapeutic target for viral infections. In addition, H4K20me3 levels are rather decreased in non-infected patients with lung cancer and chronic lung disease, suggesting that H4K20me3 may be a biomarker for worsening viral infection. Thus, the dynamics of higher-order chromatin structures in response to viral infection may serve as a therapeutic target and biomarker for infectious diseases.