HIV integration
AIDS ("acquired immune deficiency syndrome") is caused by the human immunodeficiency virus (HIV).
Additionally, HIV can also be passed from infected pregnant women to their uninfected baby during pregnancy and/or delivery ("vertical transmission"), or via breastfeeding.
As a result of HIV infection, a portion of these individuals will progress and go on to develop clinically significant AIDS.
Understanding the integration process will provide a framework for gaining insight into multiple potential sites of therapeutic intervention for HIV infection and AIDS.
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.
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.
Integrase functions are unique to retroviruses; human cells are not required to cut-and-paste pieces of DNA into the genome.
The binding takes place at specific sequences in the long terminal repeat regions.
[citation needed] 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.
Regardless of the sequence, it is believed that the presence of LEDGF/p75 results in the integrase dimers approaching each other to form a tetramer.
[citation needed] The next step, the strand transfer reaction, takes place inside the host cell nucleus and involves the critical step of inserting the HIV DNA into a selected region of the host DNA.
In addition, the two base pairs at the end of the 5’ region of the viral DNA remain unpaired after the strand transfer.
[2] This preference depends on the host chromatin binding protein LEDGF/p75 that interacts with many splicing factors.
