solution and in crystal structures. The vast surface area of the dimer interface indicates that it is biologically significant. The insertion sites on each strand of target DNA are separated by 5 base pairs, which parallel to approximately 15 Å for helical B-form DNA, implying that the catalytic domain (or the functional unit) of integrase should contain a pair of active sites separated by a like spacing. This said, the spacing among the active sites in the virtually spherical dimer is, however, apparently not very well-matched with the spacing among the insertion sites on the two strands of target DNA, as examination of crystal structures appears to reveal that the active sites in the dimers are separated by more than 30 Å when measured in a straight line through the proteins, and by an even greater distance when measured around the circumference of the dimer. Under the assumption that the dimer interface is preserved in the functional integrase multimer, at minimum a tetramer of integrase must be required for the complete integration reaction to proceed. 3. The Carboxy (C)- terminal domain : The C-terminal domain non-specifically binds DNA. Since the sites of integration into the target DNA are relatively non-specific, it is thought that this domain may work together in some fashion with the target DNA. Information retrieved from experiments with chimeric integrases show that recognition of the target site is controlled by the core domain. Cross-linking studies also suggest that the C-terminal domain works together with a subterminal region just inside the very ends of the viral DNA. During the integration process, the HIV integrase enzyme performs two key catalytic reactions. First is the 3’ processing of the HIV DNA, followed by strand transfer of the HIV DNA into the host DNA. The integration of HIV DNA can occur either in dividing or resting cells, and the HIV integrase enzyme can exist in the form of a monomer, dimer, tetramer, and possibly even higher-order forms (such as octomers). Each HIV particle has an estimated 40 to 100 copies of the integrase enzyme. Integrase functions are unique to retroviruses; human cells are not required to cut-and-paste pieces of DNA into the genome. For this reason, integrase inhibitors are prime targets for developing drug therapies for HIV infection and AIDS, since inhibition of integrase should not hamper the normal operations in human cells. HIV Integration Mechanism HIV integration is the insertion