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DNA and RNA viruses target a common subnuclear domain: many images to one structure?

Nature Reviews Microbiology volume 4, page 318 (2006)Cite this article

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Indeed, we have been the first to demonstrate that adenovirus-5 immediate-early viral proteins from the E1 and E4 transcription units (the E1B-55kd, E4-ORF6 and E4-ORF3 proteins) coordinate a dramatic morphological change of PML NBs which results in a relocation of cellular proteins that interact with PML to the viral inclusions bodies, the sites of adenovirus replication and late RNA transcription5. Contrary to the statement in the Highlighted references in the Review by Nisole et al. recently published in this journal7, we were the first to demonstrate that PML expresses antiviral activities by showing that expression of wild-type PML considerably suppressed adenovirus-5 replication in living cells5. Our mutation analysis suggested that the PML-activated repression of adenovirus-5 replication in vivo reflects biological activities that are probably linked to compartmentalized macromolecular complexes, such as the PML domain, rather than to its free protein markers such as the PML protein. Similarly, we showed that treatment of the cells with interferon (IFN)-β, which enhanced the expression of PML/Sp100, modified the molecular properties of PML domains, blocked the action of adenovirus on PML-NB dissociation and suppressed adenovirus replication. Together, these results supported a regulatory role of PML NBs in the early-to-late switch of adenovirus-5 replication5. Therefore, these results gave rise to our first ideas of a new theory of how viruses infect cells and ultimately utilize cell-regulatory proteins for their own purposes. Because cells have many ways to defend themselves against infection, a necessary role of the virus is to disarm protective mechanisms that might otherwise normally block activation of the viral programme. In addition, viruses should organize the takeover of the cellular know-how that is essential for viral growth and propagation. If a cellular 'machine' exists that coordinates signal-activated cellular responses — both at the transcription, DNA-processing and translation levels — then the virus should be evolutionary well organized to detect and take over the know-how of such a 'machine'. So, one of the major questions that emerged from these studies on adenovirus-5 and PML-NB functional and structural association was whether the PML domain serves as a common target for multiple viruses or whether this process is specific for the adenovirus-5 replication. To extend our observation to other viruses, we examined PML NBs and HIV-1 propagation properties in living cells. Contrary to the viral cycle of adenovirus-5, which is divided into an early and late phase relative to initiation of viral replication8,9,10, the HIV-1 propagation depends on a reverse transcription and a nuclear-import process that ends with virus integration into the host-cell genome11.

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Figure 1: Model depicting a mechanism for a coordinate regulation of signal transduction at the cellular level throughout distinct nuclear bodies (NBs) or domains.

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  1. Research Investigator at The Virtual Molecular Chorobiology Laboratory, 1 rue du Commandant Jean-Duhail, Fontenay-sous-Bois, 94120, France

    Vassilis Doucas

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Doucas, V. DNA and RNA viruses target a common subnuclear domain: many images to one structure?. Nat Rev Microbiol 4, 318 (2006). https://doi.org/10.1038/nrmicro1398-c1

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