Abstract
During lytic infection, DNA viruses that replicate in the nucleusof cells establish an environment that favors viral replication whileevading cellular defenses. Consequently, these viruses must engagewith cellular factors that are necessary for efficient viraltranscription and DNA replication, while disarming restrictivecellular responses to the presence of the invading pathogenicDNA. It is important to consider these events not only at thebiochemical level of protein-protein and protein-nucleic acidinteractions, but also in terms of spatial organization within thenucleus. The nucleus contains many distinct substructures,including nucleoli, chromosome territories, splicing speckles,PML Nuclear Bodies (PML NBs, also known as ND10), andtranscription sites, all of which are in a dynamic environmentinvolving the exchange of protein molecules between thestructures themselves and the general nucleoplasm [1]. DNAviruses establish their own transcription sites and replicationcompartments within the nucleus, and a topic that has been ofinterest for many years is how these virus-specific loci relate to thepreexisting cellular nuclear substructures, particularly during theearly stages of infection. Is viral genome localization random, or isit regulated in some way?Gerd Maul made a breakthrough discovery when he found thatafter their delivery into the nucleus, the genomes of many differentDNA viruses are frequently associated with PML NBs [2,3]. Theseintriguing findings posed many questions: How does thisassociation occur? What are the viral and cellular signals involved?Does the association have a positive or negative influence oninfection?
Highlights
During lytic infection, DNA viruses that replicate in the nucleus of cells establish an environment that favors viral replication while evading cellular defenses
An alternative explanation of viral genome–PML NB association is that it occurs not because either entity migrates through the nucleoplasm, but because new PML NBs are formed at the sites of the viral genomes due to the deposition of PML NB protein molecules
The issues that influence the association between DNA virus genomes and PML NBs include the virus factors that are required for the response, the properties of PML NB proteins required for their recruitment, and the actions of viral regulatory proteins that affect the stability of the recruitment
Summary
DNA viruses that replicate in the nucleus of cells establish an environment that favors viral replication while evading cellular defenses. In the case of HSV-1, a chance observation provided very strong evidence that this was the case—the viral genomes became very rapidly associated with novel PML NB–like structures in the earliest stages of infection through recruitment of PML NB proteins [4] (Figure 1). What Factors Are Involved in the Association between DNA Virus Genomes and PML NBs?
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