Studies on molecular determinants for virulence of lethal infection of infectious bursal disease virus

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Infectious bursal disease virus (IBDV) is the causative agent of immunosuppressive disease of young chicken. There are two types of IBDV based on the lethality for chicken, highly virulent and classical types. However, the molecular determinants for the difference of lethality have not been defined. In the present study, IBDV strains which show high mortality and low mortality designated as highly virulent type and classical type, respectively were used for comparative study of subcellular localization of viral structural proteins, VP2,VP3 and VP4, and nonstructureal protein VP5. In addition, cell toxicity of each viral protein was analyzed. For the VP2 and VP5, bacterial 2-hybrid system was used to determine the cellular molecules which interact with the viral proteins. Comparative study of subcellular localization of each viral protein showed that the VP5 showed differences between the highly virulent type and the classical type. Furthermore, VP5 derived from highly virulent strain showed higher cell toxixity than that of VP5 derived from classical type. Unfortunately, the cellular molecules which interact with the viral proteins were not detected. These results indicate that VP5 is responsible for the virulence of highly virulent IBDV. Previous report of the deduced amino acid sequence allignment showed 4 amino acid differences between the sequence of highly virulent type and classical type. The only 4 amino acids in VP5 may contribute to the virulence of highly virulent type of IBDV.