In this latency type, viral genes are stabilized, floating in the cytoplasm or nucleus as distinct objects, either as linear or lasso-shaped structures.
[3] The Gammaherpesvirinae subfamily is associated with episomal latency established in cells of the immune system, such as B-cells in the case of Epstein–Barr virus.
[5] In the case of herpes simplex (HSV), the virus has been shown to fuse with DNA in neurons, such as nerve ganglia[6] or neurons, and HSV reactivates upon even minor chromatin loosening with stress,[7] although the chromatin compacts (becomes latent) upon oxygen and nutrient deprivation.
[11] Advantages of episomal latency include the fact that the virus may not need to enter the cell nucleus, and hence may avoid nuclear domain 10 (ND10) from activating interferon via that pathway.
Several classes of latency reversing agents (LRAs) are under development for possible use in shock-and-kill strategies in which the latently infected cellular reservoirs would be reactivated (the shock) so that anti-viral treatment could take effect (the kill).
Expression of these latency-associated genes may function to keep the viral genome from being digested by cellular ribozymes or being found out by the immune system.
[16] An example of such a gene product is the latency associated transcripts (LAT) in herpes simplex virus, which interfere with apoptosis by downregulating a number of host factors, including major histocompatibility complex (MHC) and inhibiting the apoptotic pathway.
[18] Some of the proteins expressed by these viruses have co-evolved with host cells to play important roles in normal processes.
In a notable event, this actually happened during gene therapy through the use of retroviral vectors at the Necker Hospital in Paris, where twenty young boys received treatment for a genetic disorder, after which five developed leukemia-like syndromes.
Specifically, the presence of replication-competent HIV in resting CD4-positive T cells allows this virus to persist for years without evolving despite prolonged exposure to antiretroviral drugs.