Herpes viruses hedge their bets

Abstract

Static latency is the hallmark of all herpes viruses. The varicella zoster virus, for instance, causes varicella (chickenpox), and after a latent phase of between 5 and 40 years, it can give rise to herpes zoster (shingles). This latency and the subsequent reactivation has intrigued and puzzled virologists. Although several factors have been suggested, it is unknown what triggers reactivation. However, latency can be explained with a simple evolutionary model. Here, we demonstrate that a simple, yet efficient, bet-hedging strategy might have evolved in a number of viruses, especially those belonging to the herpes virus family and most importantly in varicella zoster virus. We show that the evolution of latency can be explained by the population dynamics of infectious diseases in fluctuating host populations.fluctuating environment ͉ disease dynamics ͉ phenotypic evolution ͉ geometric mean fitness S tatic latency (1, 2) is a characteristic feature of all herpes viruses; whereas herpes simplex 1 and 2 and varicella zoster virus (VZV) stay latent in cells of the nervous system, and cytomegalovirus and Epstein-Barr virus establish themselves in cells of the immune system (1, 2). Their latency is static in the sense that no virus is produced and that latency seems to be actively maintained by a number of viral genes (3-7). In contrast, dynamic latency (2) involves an actively replicating virus that is kept at bay through the host's response and not because of the virus's replication strategy. The latency of the HIV is an example of dynamic latency (8). Here, our main interest is in trying to understand when and why latency evolves rather than in the molecular mechanisms involved in establishing, maintaining, and controlling latency. These are very different questions, not least because the former approach already postulates that latency is a useful strategy for the virus.We focus on VZV because it displays the longest latency period and may thus serve as a canonical example for latent behavior. During the latent phase, VZV resides in neurons in the dorsal root and trigeminal ganglia (5, 6). It does not seem to replicate until it reactivates and the clinical symptoms of herpes zoster develop; reactivation is not normally associated with a particular inciting event (2). Waning immunity, predominantly with age, has been suggested as a factor that can trigger reactivation (2, 4), especially early reactivation (9). VZV [like herpes simplex virus (HSV) 1 and HSV2] can, however, reactivate even in the presence of cellular and humoral immune response (9, 10). Exposure to chickenpox can be ruled out as a likely cause for reactivation, as the epidemiology of shingles does not follow the periodic pattern typical for chickenpox (2, 9). It therefore seems that static latency has evolved as an active strategy of the virus (1), where the virus colonizes immunoprivileged sites and stays dormant until reactivation (1, 2, 7, 10).Previously, research into latency has focused largely on molecular mechanisms of latency and reactivation o...

The role of migration in the evolution of phenotypic switching

“…For example, a pattern of mutation rates may result in variation that enables phenotypes to switch from one form to another. This phenotypic or stochastic switching has been observed in a variety of organisms such as viruses [3], yeast [4][5][6] and bacteria [7][8][9].…”

Stochasticity enhances the gaining of bet-hedging strategies in contact-process-like dynamics

“…Later, it was conjectured that living organisms may employ bet-hedging strategies to decrease their risk in unpredictable environments [5,[9][10][11][12]. This idea has been empirically confirmed in bacterial and viral communities [2][3][4][13][14][15][16], in insects [17], in seed-dispersal strategies developed by plants [18][19][20], and in a wealth of other examples in population ecology, microbiology, and evolutionary biology [9].…”

Exact Results for the Evolution of Stochastic Switching in Variable Asymmetric Environments

“…Maintenance of phenotypic diversity has mainly been considered a bet-hedging strategy that can maximize the fitness of the genotype in uncertain environments (Stumpf et al 2002;Evans and Dennehy 2005;Beaumont et al 2009), but alternative uses have also been proposed (Ackermann et al 2008). Maintaining phenotypic diversity at all times means that some fraction of the population is always maladapted, but when the environment changes, the previously maladapted subpopulation becomes the fitter.…”