REMOVAL OF ZINC IS REQUIRED FOR PROCESSING OF THE MATURE NUCLEOCAPSIDPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS, TYPE-1, BY THE VIRAL PROTEASE

In human immunodeficiency virus, RNA selection and packaging during as sembly involve the two retroviral-type fingers of the nucleocapsid pro tein that are held in a constrained configuration by coordinated zinc ions, In this report, we demonstrate that the nucleocapsid protein in a metal bound state is resistant to cleavage by the viral protease, bu t upon removal of zinc ions by chelating agents, it is hydrolyzed with in the first zinc finger between Phe-16 and Asn-17. However, 3-nitroso benzamide and cupric ions, which release zinc through oxidation of the cysteine residues of the finger, render the nucleocapsid protein resi stant to cleavage. Since protease inhibitors and 3-nitrosobenzamide re strict processes relating to steps early in infection, the cleavage of the nucleocapsid protein may represent an essential event that can be exploited for the design of novel antiviral agents.