HIV1 Integrase

HIV-1 Integrase is a crucial enzyme in the life cycle of the Human Immunodeficiency Virus type 1 (HIV-1). It facilitates the integration of viral DNA into the host cell genome, a vital step for viral replication and persistence. Recombinant HIV-1 Integrase refers to the enzyme produced through recombinant DNA technology, which allows for its study and use in various research and therapeutic applications.

HIV-1 Integrase is composed of three domains:

1. N-terminal domain (NTD): Involved in binding to viral DNA.
2. Catalytic core domain (CCD): Contains the active site responsible for the enzyme’s catalytic activity.
3. C-terminal domain (CTD): Plays a role in binding to host DNA.

The enzyme catalyzes two critical reactions:

1. 3’-end processing: Cleaves two nucleotides from the 3’ ends of the viral DNA.
2. Strand transfer: Integrates the processed viral DNA into the host genome.

Recombinant HIV-1 Integrase is produced by inserting the integrase gene into an expression vector, which is then introduced into a host cell (commonly E. coli). The host cells express the integrase protein, which can be purified for research purposes. This recombinant protein is essential for studying the enzyme’s structure, function, and interactions with inhibitors.

HIV-1 Integrase is a key player in the viral replication cycle. After the viral RNA is reverse-transcribed into DNA, integrase facilitates the integration of this viral DNA into the host cell’s genome. This integration is necessary for the production of new viral particles and the establishment of a persistent infection.

Integrase inhibitors are a class of antiretroviral drugs that target the integrase enzyme, preventing the integration of viral DNA into the host genome. These inhibitors are crucial components of highly active antiretroviral therapy (HAART) for HIV/AIDS treatment. There are two main types of integrase inhibitors:

1. Integrase Strand Transfer Inhibitors (INSTIs): Bind to the catalytic core domain and block the strand transfer step.
2. Non-catalytic Integrase Inhibitors (NCINIs): Target other regions of the enzyme and inhibit its function through different mechanisms .

Recombinant HIV-1 Integrase is extensively used in research to understand the enzyme’s structure, function, and interactions with various inhibitors. Studies on integrase have led to the development of several FDA-approved integrase inhibitors, such as raltegravir, elvitegravir, and dolutegravir. Ongoing research aims to develop new inhibitors with improved efficacy and resistance profiles .