In this paper, we revealed that IE2－an early gene product of the baculovirus－could form unique nuclear bodies for the strong trans-activation of various promoters in mammalian cells. Heat shock proteins (HSPs) were found to be one of the major IE2-associated proteins. Our experiments show that HSPs are greatly induced by IE2 and are crucial for the trans-activation function of IE2. These observations reveal that HSPs do not function directly to assist the formation of the nuclear body structure, but may rather protect IE2 from proteasome degradation. We also show that HSPs were stimulated and required to determine IE2 protein levels, in insect cells infected with baculovirus. Thus, we demonstrate a unique feature in that IE2 can function in both insect and non-host mammalian cells to stimulate HSPs, which associated with IE2 stabilization and lead to the protection of the its strong gene activation function in mammalian cells and during viral infection in insect cells, IE2 could also strongly stimulate HSPs and ultimately affect viral replication.