Before integration occurs, HIV must convert its RNA genetic material into DNA. The enzyme reverse transcriptase performs this conversion, producing viral DNA that can enter the nucleus. Integrase then helps insert the viral DNA into the host cell's genetic material.
The main stages involved include:
The integrated viral DNA is called a provirus. Once established in the host genome, it can be transcribed using the cell's machinery, producing viral RNA and proteins needed for further HIV replication.
Integrase is a viral enzyme that plays a central role in inserting HIV DNA into the host cell genome. It operates as part of a protein and DNA complex called the intasome. This complex coordinates the reactions required for viral DNA integration. Researchers study the structure and activity of integrase to understand how the virus replicates and how medicines can interfere with this process.
Integrase strand transfer inhibitors, commonly known as INSTIs, are a class of antiretroviral medicines that target HIV integrase. They prevent the strand transfer step required for integrating viral DNA into host cell DNA. By interfering with this stage, these medicines help prevent HIV from completing its replication cycle.
Examples of integrase inhibitors include:
These medicines are used as part of HIV treatment regimens, depending on clinical considerations and treatment guidelines.
Integration also helps explain why HIV treatment does not eliminate every infected cell containing viral genetic material. Some infected cells, including long-lived CD4 T cells, can carry integrated HIV DNA and remain present during antiretroviral therapy. In certain cells, viral activity can become limited, allowing HIV genetic material to persist in a latent state.
Antiretroviral therapy suppresses HIV replication but does not routinely remove all integrated viral DNA from infected cells. Researchers continue to investigate viral reservoirs, integration patterns, and approaches that could support future HIV cure strategies.
Research into HIV integration focuses on understanding the molecular interactions between integrase, viral DNA, and host cell DNA. Scientists investigate how the integration complex is formed, how integration sites are selected, and how integrase inhibitors interfere with the process.
This research supports the development of antiretroviral medicines and contributes to a broader understanding of HIV biology.