Single viral genome analysis reveals escape mechanisms for adenoviruses from nuclear antiviral sensors and effectors (Komatsu et al. 1-3)
Latency and lytic replication are two hallmarks of nuclear replicating DNA viruses. In recent years it became evident that the chromatin structure of the viral genome is the underlying cause to distinguish between repressive/latent state and transcriptional active/lytic state. In this context the first hours of an infection have been suggested to play a crucial role in how the cell nucleus perceives and reacts to an invading genome. Based on studies in the herpes simplex virus it was suggested that PML nuclear bodies and its constituents such as the chromatin remodeling complex Daxx/ATRX, SP100 or PML are major effectors targeting incoming genomes to establish a repressive chromatin structure on the viral genome with the goal to suppress viral gene expression. The observation that knockdown of individual PML-NB components and/or nuclear DNA sensors such as IFI16 have pro-viral functions and the observation that viral genomes of other viral families also associate with PML nuclear bodies was used to generalize the notion that PML nuclear bodies are ubiquitous, IFN inducible antiviral factors against invading viral genomes.
In this series of three manuscripts by Komatsu et al. we oppose this generalized view. First we developed (1) an imaging system for individual incoming adenoviral genomes to study the nuclear antiviral response. In subsequent studies we show that for adenoviruses (2) neither PML nuclear bodies nor (3) IFN treatment nor other known antiviral factors such as IFI16, PH13/SPOC or SP100 isoforms target invading adenovirus genomes. We conclude that adenoviruses, different from herpesviruses, have developed mechanisms to evade a large repertoire of nuclear antiviral sensors and effectors providing a rational for their efficient lytic replication. Our data also show that PML nuclear bodies react differentially to viral genomes when exposed to different virus families and show the need for detailed in depth studies and the requirement for developing suitable experimental systems to visualize individual viral genomes at the single cell level.
(1) A Method for Visualization of Incoming Adenovirus Chromatin Complexes in Fixed and Living Cells. Komatsu T, Dacheux D, Kreppel F, Nagata K, Wodrich H. PLoS One. 2015 Sep 2;10(9)
(2) An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies. Komatsu T, Nagata K, Wodrich H. J Virol. 2015 Nov 25;90(3):1657-67. doi: 10.1128/JVI.02545-15.
(3) Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes. Komatsu T, Will H, Nagata K, Wodrich H. Biochem Biophys Res Commun. 2016 Mar 22.