Herpesvirus Latency

Herpesviruses are large, enveloped viruses that have a linear, double stranded DNA genome. More than 200 herpesviruses have been discovered and at least one has been found in every animal species investigated. A hallmark of herpesviruses is that they establish a life-long persistent infection in the host termed latency. During latency, the viral genome is maintained in infected cells in the absence of virion production. In long lived cells such as neurons, the virus genome is efficiently maintained as a circular episome. However, deposition of the latent virus genome in replicating cells requires replication of the virus genome and distribution into the daughter cells. This can either be achieved by tethering the virus episome to host chromosomes, as shown for several lymphotropic herpesviruses such as Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KHSV). Alternatively, several herpesviruses including human herpesvirus 6 (HHV-6) and Marek’s disease virus (MDV) have been shown to integrate their genome into the telomeres of host cells. Both mechanisms allow maintenance of the virus genome in the host despite a short lifespan of these cells, however more work is need to fully understand how herpesviruses maintain their genome in latently infected cells.

During the establishment of latency, the herpesvirus genome is (mostly) silenced to avoid initiation of lytic replication. The mechanisms involved in the establishment and maintenance of latency are still not completely understood. Epigenetic changes present on the virus genome certainly contribute to transcriptional silencing and is a focused area of research in the field. Reactivation of the virus in latently infected cells results in the production of infectious virus particles and is often associated with severe clinical symptoms. However, the stimuli resulting in reactivation are poorly understood and there are no treatments available that block herpesvirus reactivation.

This Frontiers Research Topic is dedicated to the importance of herpesvirus latency and reactivation. We welcome original research articles, opinions, perspectives, methods and reviews highlighting the current advances in our understanding of herpesvirus latency and reactivation.