Which HIV enzyme is responsible for integrating viral DNA into the host chromosome?

Explanation

## HIV Integrase: The Integration Enzyme **Key Point:** HIV integrase is the viral enzyme that catalyzes the integration of reverse-transcribed HIV DNA into the host cell chromosome, establishing persistent infection. ### The Integration Process ```mermaid flowchart LR A[HIV RNA genome]:::outcome --> B[Reverse transcriptase<br/>converts to DNA]:::action B --> C[Pre-integration complex<br/>enters nucleus]:::action C --> D[Integrase catalyzes<br/>strand transfer]:::action D --> E[Viral DNA integrated<br/>into host chromosome]:::outcome ``` ### Integrase Mechanism Integrase performs three catalytic steps: 1. **3' Processing:** Removes dinucleotide from 3' end of viral DNA 2. **Strand Transfer:** Inserts viral DNA into host chromosome 3. **Gap Repair:** Host cell machinery fills in remaining gaps ### Clinical Significance **High-Yield:** Integrase inhibitors (e.g., dolutegravir, bictegravir, raltegravir) are among the most potent and well-tolerated antiretroviral drugs, with high genetic barrier to resistance. ### Why Integration Matters - Creates a **provirus** — integrated viral DNA that replicates with the host cell - Establishes **latent infection** in long-lived cells (memory CD4+ cells, macrophages) - Explains why HIV cannot be cured by antiretroviral therapy alone - Integration is essentially irreversible without cell death **Mnemonic:** **RIPE** = Reverse transcriptase, **I**ntegrase, **P**rotease, **E**nvelop proteins — the four key HIV enzymes/proteins. [cite:Harrison 21e Ch 197]