Nuclear transport of the major capsid protein is essential for adeno-associated virus capsid formation

Adeno-associated virus capsids are composed of three proteins, VP1, VP2, an d VP3. Although VP1 is necessary for viral infection, it is not essential f or capsid formation. The other capsid proteins, VP2 and VP3, are sufficient for capsid formation, but the functional roles of each protein are still n ot well understood. By analyzing a series of deletion mutants of VP2, we id entified a region necessary for nuclear transfer of VP2 and found that the efficiency of nuclear localization of the capsid proteins and the efficienc y of virus-like particle (VLP) formation correlated well. To confirm the im portance of the nuclear localization of the capsid proteins, we fused the n uclear localization signal of simian virus 40 large T antigen to VP3 protei n. We show that this fusion protein could form VLP, indicating that the VP2 -specific region located on the N-terminal side of the protein is not struc turally required. This finding suggests that VP3 has sufficient information for VLP formation and that VP2 is necessary only for nuclear transfer of t he capsid proteins.