Chromatin at the intersection of viral infection and DNA damage

Abstract

During infection, viruses cause global disruption to nuclear architecture in their attempt to take over the cell. In turn, the host responds with various defenses, which include chromatin-mediated silencing of the viral genome and activation of DNA damage signaling pathways. Dynamic exchanges at chromatin, and specific post-translational modifications on histones have recently emerged as master controllers of DNA damage signaling and repair. Studying viral control of chromatin modifications is identifying histones as important players in the battle between host and virus for control of cell cycle and gene expression. These studies are revealing new complexities of the virus-host interaction, uncovering the potential of chromatin as an anti-viral defense mechanism, and also providing unique insights into the role of chromatin in DNA repair.

Figure 1. Viral control of cellular histone modifications

Chromatin remodeling proteins and histone post-translational modifications known to be targeted by viruses are depicted. Histone post-translational modificatons which have a known role in DNA repair are shown in bold. Effects of the viral proteins (boxed) on the chromatin-related substrates are indicated by the shaded trianges. Red triangles indicate interactions that are inhibitory to the pathways or cellular factors targeted and green triangles denote interactions that promote the activity of the pathways or cellular factors targeted. For simplicity, not all histone targets of the cellular enzymes are shown. The interactions depicted are limited to those covered in this review and many more examples of associations between viral and cellular proteins exist.