Suppressive activity of a viral histone H4 against two host chromatin remodelling factors: lysine demethylase and SWI/SNF.

Histone H4, a nucleosome subunit in eukaryotes, plays crucial roles in DNA package and regulation of gene expression through covalent modification. A viral histone H4 encoded in Cotesia plutellae bracovirus (CpBV), a polydnavirus, is called CpBV-H4. It is highly homologous to other histone H4 proteins excepting 38 extra amino acid residues in the N terminus. CpBV-H4 can form octamer with other histone subunits and alter host gene expression. In this study, CpBV-H4 was transiently expressed in a natural host (Plutella xylostella) and its suppressive activity on host gene expression was evaluated by the suppressive subtractive hybridization (SSH) technique. The SSH targets down-regulated by CpBV-H4 were read with the 454 pyrosequencing platform and annotated using the genome of P. xylostella. The down-regulated genes (610 contigs) were annotated in most functional categories based on gene ontology. Among these SSH targets, 115 genes were functionally distinct, including two chromatin remodelling factors: a lysine-specific demethylase (Px-KDM) and a chromatin remodelling complex [Px-SWI/SNF (SWItch/Sucrose Non-Fermentable)]. Px-KDM was highly expressed in all tested tissues during the entire larval period. Suppression of Px-KDM expression by specific RNA interference (RNAi) significantly (P<0.05) reduced haemocyte nodule formation in response to immune challenge and impaired both larval and pupal development. Px-SWI/SNF was expressed in all developmental stages. Suppression of Px-SWI/SNF expression by RNAi reduced cellular immune response and interfered with adult metamorphosis. These results suggest that CpBV-H4 can alter host gene expression by interfering with chromatin modification and remodelling factors in addition to its direct epigenetic control activity.