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

Tarakhovsky, Alexander; Prinjha, Rab K.

The recent studies of 2,278 viral genomes comprising 41 viral families (Selenko et al., 2008) show striking variation in the amount of protein disorder both within and between viral families (from 2.9 to 23.1% of residues). Remarkably, the degree of disorder correlates negatively with the genome sizes within each of the five main viral types (single-stranded [ss]DNA, double-stranded [ds]DNA, ssRNA + , dsRNA, retroviruses), with the exception of negative single-stranded RNA viruses, in which disorder increases with the size of the genome. More than 20 small viruses that encode five or fewer proteins have 50% or more disordered residues in their proteomes (Xue et al., 2014a) . As the proteome size increases among different viruses, the fractions of disordered residues converges to 20-40%. Protein disorder is highly abundant in human viruses such as HCV, HIV-1 (Xue et al., 2012) , and human papillomaviruses (Uversky et al., 2006; Fan et al., 2014; Xue et al., 2014b) , and the varying magnitude of disorder may enable viruses to impact numerous host factors. Additionally, the lack of inherent structure reduces the constraints of protein function and allows for creation of novel protein motifs that could be used by the virus to subvert host functions (Selenko et al., 2008; Sanjuán and Domingo-Calap, 2016) . It has been also suggested that flexible structures may help viral proteins to evade the host immune system (Goh et al., 2008 (Goh et al., , 2009 (Goh et al., , 2012 (Goh et al., , 2013 . In particular, protein disorder may help viruses tolerate a high mutation rate and hence adapt to the host defenses. Additionally, a lack of structural constraints is supposed to promote a multiplicity of viral protein interactions with the host proteins and target multiple elements of the host cell defense system (Xue et al., 2014a ).