Which is the most common structural protein of HIV that is targeted by neutralizing antibodies and serves as the primary attachment protein for host cell entry?

Explanation

## HIV Surface Glycoproteins and Their Roles **Key Point:** gp120 is the outermost envelope glycoprotein of HIV and is the primary target of neutralizing antibodies because it directly binds to CD4 receptors on host cells. ### Structural Organization of HIV Envelope The HIV envelope consists of two main glycoproteins: | Protein | Location | Function | Antibody Target | | --- | --- | --- | --- | | **gp120** | Outer surface | CD4 and co-receptor (CCR5/CXCR4) binding | Primary neutralizing antibody target | | **gp41** | Transmembrane | Membrane fusion; exposed after gp120 binding | Secondary neutralizing antibody target | ### Why gp120 is Most Commonly Targeted 1. **First point of contact:** gp120 is the outermost protein and makes initial contact with CD4 receptors on target cells (CD4+ T cells, macrophages, dendritic cells). 2. **Immunological significance:** The humoral immune response predominantly generates antibodies against gp120 due to its accessibility on the virion surface. 3. **Vaccine development focus:** Most HIV vaccine candidates (RV 144 trial, HVTN 702) have targeted gp120 epitopes. 4. **Conformational changes:** gp120 undergoes conformational changes upon CD4 binding, exposing gp41 and co-receptor binding sites. **Clinical Pearl:** The gp120-CD4 interaction is so critical that it is the basis for CCR5 antagonist (maraviroc) and fusion inhibitor (enfuvirtide) mechanisms — these drugs block the conformational changes needed for gp41 exposure. **High-Yield:** In NEET PG, remember: **gp120 = attachment (CD4 binding) → gp41 = fusion (membrane merger)**. Neutralizing antibodies against gp120 prevent the initial step of infection. ### Other HIV Proteins (Not Primary Antibody Targets) - **p24 (capsid protein):** Internal structural protein; detected in serum during acute infection but not a neutralizing antibody target. - **p7 (nucleocapsid protein):** Binds and protects viral RNA; not exposed on virion surface. [cite:Harrison 21e Ch 197]