A viral histone H4, CpBV-H4, is encoded in the Cotesia plutellae bracovirus (CpBV) genome. This polydnavirus is symbiotic with C. plutellae, an endoparasitoid wasp. When the wasp parasitizes its host, Plutella xylostella. the symbiotic CpBV is delivered to host hemocoel and infects different internal tissues. CpBV-H4 encoded in the virus exhibits high sequence similarity to host histone H4, except for an extended N-terminal tail (38 amino acids long). When the CpBV-H4 cloned in a eukaryotic expression vector was transiently expressed in P. xylostella and a nonhost, Spodoptera exigua, it clearly inhibited several immune-associated genes, including cecropin, gloverin, serpin, apolipophorin Ill, and transferrin. However, its truncated construct. prepared by deleting 38 amino acids at the N-terminal tail, lost its inhibitory activity against immune-associated genes of the both species. This study has verified an inhibitory activity of CpBV-H4 against host immune-associated genes and has provided a possibility to expand its activity spectrum to the genes of other insect species.