of HIV genetic material into the genome of the infected cell. The process of HIV integration involves six sequential steps: Binding of HIV Integrase to HIV DNA The first step of the integration process occurs in the cytoplasm of the host cell following the completion of reverse transcription of the HIV RNA into c-DNA. This step involves the binding of integrase - most likely in the dimer form - to each end of the newly formed HIV c-DNA. The binding takes place at specific sequences in the long terminal repeat regions. The integrase-HIV DNA complex is part of an intracellular nucleoprotein particle known as the "preintegration complex" (PIC). This complex consists of linear HIV DNA, viral proteins, and host proteins. The viral proteins include integrase, nucleocapsid, matrix, viral protein R (Vpr), and reverse transcriptase. Several host proteins can also form part of this complex, although it is unclear whether some or all join the preintegration complex prior to nuclear transport. Processing of the HIV DNA 3’ ends In the second step of the integration process, which also takes place in the host cytoplasm, the integrase dimer cleaves the viral DNA at each 3’ end. This cleavage reaction removes GT dinucleotides on the 3’-side of a conserved CA dinucleotide region. The cleavage of the dinucleotide at each viral DNA 3’-end generates a dinucleotide 5’ "overhang" and a reactive intermediate that contains a 3’-hydroxyl group. This 3’ processing step is the first of two key catalytic reactions performed by the integrase enzyme, and it prepares the viral DNA for integration into the host DNA. In an alternative view of the DNA binding and 3’-processing reaction, the tetramer form of integrase (not the dimer) binds to the ends of the HIV DNA, and then cleaves the 3’ ends. Translocation of HIV integrase to the host cell nucleus (Nuclear Translocation) In the third step of the integration process, the preintegration complex is transported into the nucleus of the host cell, entering through one of the nuclear pore complexes. Binding of the preintegration complex to the host DNA Inside the nucleus, the host protein lens epithelium-derived growth factor/p75, commonly referred to in abbreviated form as LEDGF/p75, binds to the preintegration complex and the host DNA. The LEDGF/p75 serves as a tethering protein (or bridge) between the preintegration complex and the host DNA. The sequence of binding of the LEDGF/p75, the host DNA, and the preintegration