Regarding HIV-1 replication and the role of viral enzymes, all of the following statements are true EXCEPT:

## HIV-1 Replication and Viral Enzymes ### Correct Statements (Options 0, 1, 2) **Key Point:** HIV-1 replication depends on three essential enzymes: #### Reverse Transcriptase (RT) **High-Yield:** RT has two catalytic activities: 1. **RNA-dependent DNA polymerase** — synthesizes the first DNA strand using the viral RNA as template 2. **RNase H** — degrades the RNA strand, leaving single-stranded DNA 3. **DNA-dependent DNA polymerase** — synthesizes the complementary DNA strand The intermediate product is a **DNA-RNA hybrid**, which is then converted to **double-stranded DNA (dsDNA)**. #### Integrase **Clinical Pearl:** Integrase catalyzes two sequential reactions: 1. **3' processing** — removes dinucleotides from the 3' end of the viral DNA 2. **Strand transfer** — inserts the processed viral DNA into the host chromosome **Warning:** Integration occurs at **relatively random sites** across the genome (though some preference for actively transcribed regions). This is distinct from some other retroviruses (e.g., MLV) that show more specific integration patterns. #### Protease **Mnemonic:** **P = Polyprotein Processor** — Protease cleaves Gag (p55 → p24, p17, p7, p6) and Pol (p110 → RT, p31 integrase, p11 protease) into mature, functional proteins. ### Why Option 3 is INCORRECT **Warning:** The viral envelope is **NOT** derived from the host cell **nucleus**. HIV-1 buds from the **plasma membrane** (cell surface), acquiring the lipid bilayer from the **cell membrane**, not the nuclear membrane. **Key Point:** The budding process: 1. Viral Gag proteins assemble at the plasma membrane 2. The nascent virion buds outward, enveloping itself in the host cell **plasma membrane** 3. Viral glycoproteins (gp120/gp41) are inserted into the envelope **during or before budding**, not post-budding 4. The mature virion is released with a lipid bilayer derived from the **plasma membrane** | Feature | Correct | Option 3 (Incorrect) | | --- | --- | --- | | Envelope source | Plasma membrane (cell surface) | Nuclear membrane | | Glycoprotein insertion | During/before budding | Post-budding | | Budding site | Plasma membrane | (Implies nuclear membrane) | ## HIV-1 Budding and Maturation ```mermaid flowchart TD A[Gag/Pol translation in cytoplasm]:::outcome --> B[Gag/Pol traffic to plasma membrane]:::action B --> C[Gag multimerization at PM]:::action C --> D[Virion buds, acquires PM lipid bilayer]:::action D --> E[Glycoproteins gp120/gp41 embedded in envelope]:::outcome E --> F[Protease cleaves Gag/Pol during/after release]:::action F --> G[Mature, infectious virion]:::outcome ``` [cite:Harrison 21e Ch 189]