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

Tarakhovsky, Alexander; Prinjha, Rab K.

In case of pathogenic viruses such as influenza, suppression of type I IFN expression and numerous IFN-stimulated genes (ISGs) dominates the infected cell phenotype (García-Sastre, 2017). With type I IFN and ISGs suppressed, the influenza virus can survive and use cell biosynthetic machinery to generate new viral particles. In the case of pathogenic flaviviruses such as dengue, yellow fever, or HCV, infection not only suppresses IFN/ISG but also results in accumulation of a new ER-associated lipid compartment that supports viral infection. To achieve this aim, the flaviviruses alter expression of genes that control lipid accumulation by fatty acid oxidation (Bozzao et al., 1989) . These gene expression changes alter lipid metabolism in a way that facilitates the build-up of a membranous web-a de novo-generated intracellular compartment that supports virus RNA replication and assembly of the viral particles (Martín-Acebes et al., 2016) . HVB, a double-stranded DNA virus of the Hepadnaviridae family, encodes a regulatory X protein, HBx, that triggers lipogenesis and ensuing generation of the lipid vesicles that support virus replication (Na et al., 2009; You et al., 2013) . Human cytomegalovirus infection also induces major metabolic reprogramming, thus stimulating broad-spectrum RNA and DNA synthesis associated with an increase in cellular ribosome numbers (Tanaka et al., 1975) , as well as increased glucose uptake and glycolysis in infected fibroblasts (Landini, 1984) .