# Demonstration: HIV Virus Architecture

This demonstration uses Chimera 1.6 session file hiv-session.py in the data subdirectory.

## Electron Tomography of HIV Virus

- Colors are artificial, only gray levels (density) from electron microscope.
  - Blue is lipid envelope cut in half.
  - Red is "core" particle containing RNA.
  - Yellow is debris -- extra proteins left-over when core was made.
- Virus diameter 110 nanometers.
- Smallest blobs are about the size of one protein, several thousand atoms.
- Resolution is too low to see arrangement of molecules.
- Journal article PubMed 16407061.

## Space Navigator

- Space navigator device allows rotation and translation in 3 dimensions.
- Make sure USB cord points forward when holding device.
- Push down to move modes down, towards you to zoom in, twist to rotate.
- Left button on space navigator recenters models.
- Right button toggles simultaneous rotation and translation mode. Default is not to rotate and translate at same time for easier control.

## HIV Core

Choose "core" models in Model Panel and use "Show Only" button.

- Each blob is a protein.
  - Yellow is capsid protein arranged in 6-protein rings.
  - Purple is capsid protein arranged in 5-protein rings.
  - Orange is cyclophilin A, a human protein needed by the virus.
  - Rainbow colors are capsid protein shown at higher resolution.
- Journal article PubMed 21248851.

## HIV Protein Arrangment

Optional demo segment.

- Core shell consists of 12 pentamers of capsid protein and a few hundred hexamers.
- 5 pentamers and pointy end and 7 pentamers at wide end create distinctive conical shape.
- Has exactly the cone angle seen in electron microscopy.

## Atomic Model of Capsid Hexamer

Show full core model, zoom in on hexamer, then show only hexamer.

- 6 copies of capsid protein (PubMed 19523676).
- Different colors is to easily see boundaries between molecules.
- Curly ribbons are protein backbone.
- Thin lines are bonds betweeen atoms.
- Dots are water molecules.

## Drugs

Use Model Panel to show two drug models.

- CAP-1 drug, Univeristy of Maryland (PubMed 17826792).
- Other drug developed by Pfizer (PubMed 21170360).
- These two drugs bind in different locations.
- These drugs prevent the protein from forming hexamers and pentamers.
- Drug resistant strains arise after about 1 week.
- Neither drug is used clinically.
- HIV mutates rapidly so most HIV inhibitors do not make it to market.

## HIV Genome

Optional demo segment.

Show core models. Use side view near clip plane to cut wide end of particle. Show RNA model. Show nucleocapsid model.

- HIV core contains the virus RNA genome, about 9000 nucleotides.
- RNA is covered with 1000 copies of HIV nucleocapsid protein.
- Two copies of RNA inside core.
- Small numbers of other proteins in core (reverse transcriptase, integrase, tRNA primer, ...)