Herpesvirus Latency: On the Importance of Positioning Oneself

The nucleus is composed of multiple compartments and domains, which directly or indirectly influence many cellular processes including gene expression, RNA splicing and maturation, protein post-translational modifications, and chromosome segregation. Nuclear-replicating viruses, especially herpesviruses, have co-evolved with the cell, adopting strategies to counteract and eventually hijack this hostile environment for their own benefit. This allows them to persist in the host for the entire life of an individual and to ensure their maintenance in the target species. Herpesviruses establish latency in dividing or postmitotic cells from which they can efficiently reactivate after sometimes years of a seemingly dormant state. Therefore, herpesviruses circumvent the threat of permanent silencing by reactivating their dormant genomes just enough to escape extinction, but not too much to avoid life-threatening damage to the host. In addition, herpesviruses that establish latency in dividing cells must adopt strategies to maintain their genomes in the daughter cells to avoid extinction by dilution of their genomes following multiple cell divisions. From a biochemical point of view, reactivation and maintenance of viral genomes in dividing cells occur successfully because the viral genomes interact with the nuclear architecture in a way that allows the genomes to be transmitted faithfully and to benefit from the nuclear micro-environments that allow reactivation following specific stimuli. Therefore, spatial positioning of the viral genomes within the nucleus is likely to be essential for the success of the latent infection and, beyond that, for the maintenance of herpesviruses in their respective hosts.