DNA in the eukaryotic nucleus is packaged into highly organized chromatin. The basic structural unit of chromatin is the nucleosome, which consists of approximately 146 base pairs of DNA wrapped around a histone octamer core containing two molecules each of core histones H2A, H2B, H3, and H4. Histone covalent modification at the protruding N-terminal region from the nucleosomal core can change the chromatin conformation in order to regulate gene expression. A viral H4 was found in the genome of Cotesia plutellae bracovirus (CpBV). The obligate host of the virus is an endoparasitoid wasp, C. plutellae, which parasitizes the diamondback moth, Plutella xylostella, and interrupts host development and immune reactions. CpBV-H4 has been regarded as an immunosuppressive gene. Its extended N-terminal region contains nine lysine residues which are the target for modification. Previous report showed that CpBV-H4 inhibited hemocyte-spreading after transient expression. Here, transient expression of truncated CpBV-H4 (without N-terminal region) did not show high inhibitory effects on hemocyte-spreading. Moreover, the truncated CpBV-H4 induced acetylation of nucleus histone H4. Host H4 was found to be decreased in transcription after parasitization compared to nonparasitized larvae. Atransient expression of CpBV-H4 significantly inhibited host H4 transcription, suggesting a role of CpBV-H4 in controlling gene expression. Point mutagenesis study showed that two lysines (K6 and K16) of CpBV-H4 were found to have high inhibitory effects on hemocyte spreading. These results indicate the importance of CpBV-H4 and its N-terminal region to control gene expression and suppress host immunity.