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HIV integration


AIDS ("acquired immune deficiency syndrome") is caused by the human immunodeficiency virus (HIV). Individuals with HIV have what is referred to as a "HIV infection". When infected semen, vaginal secretions, or blood come in contact with the mucous membranes or broken skin of an uninfected person, HIV may be transferred to the uninfected person ("horizontal transfer"), causing another infection. 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.

HIV is a retrovirus, which comprise a large and diverse family of RNA viruses that make a DNA copy of their RNA genome after infection of a host cell. An essential step in the replication cycle of HIV-1 and other retroviruses is the integration of this viral DNA into the host DNA. The RNA genome of progeny virions and the template for translation of viral proteins are made when the integrated viral DNA is transcribed.

The integration of HIV DNA into the host DNA is a critical step in the HIV life cycle. Understanding the integration process will provide a framework for gaining insight into multiple potential sites of therapeutic intervention for HIV infection and AIDS. HIV’s enzyme for inserting the DNA version of its genome into the host cell DNA is called its "integrase". HIV-1 integrase catalyzes the “cut-and-paste” action of clipping the host DNA and joining the proviral genome to the clipped ends. This protein, which is 288 amino acids in length, contains three “domains”, in this order:


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