Drawing on disorder: How viruses use histone mimicry to their advantage

Tarakhovsky, Alexander; Prinjha, Rab K.

There are an estimated 37.2 trillion cells in the human body (Bianconi et al., 2013) , organized into anatomically and functionally defined tissues that maintain their phenotypic stability in the face of environmental pressure, stochastic changes in gene and protein expression, and even structural genetic alterations (Barabási and Oltvai, 2004; Stelling et al., 2004 ). Yet, cells can be challenged with extreme perturbations caused by invasion of foreign life forms (pathogens) that aim to exploit the cell's resources to ensure their own replication. Viruses, both DNA and RNA forms, represent the most impactful types of pathogens with respect to the interference with intracellular environment. Although bacterial species and protozoans mostly use extracellular resources to support their replication, viral replication requires cooperation from the host cell's biosynthetic processes and concomitant suppression of the host antiviral response (Virgin, 2014; Pfeiffer and Virgin, 2016) . To understand the degree to which viruses impact on human life, one needs to consider the actual number of viruses that exist in the biosphere. Although many of the calculations can be seen as arbitrary, it is estimated that there are ∼100 million different viruses populating 1,740,330 species of vertebrates, invertebrates, plants, lichens, mushrooms, and brown algae (Woolhouse et al., 2012) . All adult humans are chronically infected with RNA and DNA viruses-most originating in animals-that could be either pathogenic or innocuous (Virgin et al., 2009; Cadwell, 2015) . Each human harbors an estimated 8-12 chronic infections (Virgin et al., 2009) . The size of the mammalian virome is not known, but the fact that there are 10 8 -10 9 viruses, which represent multiple viral species, per gram of human feces offers a glimpse into the complexity and abundance of viruses in the human body (Mokili et al., 2012; Reyes et al., 2012) . This number significantly underestimates viruses residing outside of the gastrointestinal tract; with these considered, the total number of viruses within the human body is probably closer to ∼10 15 (Mokili et al., 2012; Nikolich-Zugich et al., 2017) .