HIV Spike Demo Storyboard

Storyboard for HIV spike demonstration for RBVI advisory committee meeting on November 13, 2009.

Aim of demonstration

Aim is to show EM, sequence, and network visualization tools applied to a single biological problem.

Biological Problem

The specific biological problem is to understand interactions of broadly neutralizing antibodies (bNAb) with HIV spike proteins gp120 and gp41. The spikes recognize CD4 receptors on human T-cells to identify and infect those cells. The motivation is to develop an HIV vaccine which works by eliciting production of these antibodies. This month two new bNAbs were reported that are effective against more HIV strains and at lower antibody concentrations than the previously known half-dozen bNAbs.

Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target.
Walker LM, et al.
Science. 2009 Sep 3 ​PubMed 19729618

Things to show

Schematic of HIV virus architecture

EM tomography view of HIV particles (Stephen Fuller lab).

Will show some tomography data and how to get from A to B in above figure.

There are about 15 gp120 crystal structures, all monomeric. The 2 new bNAbs bind only to trimeric gp120 spikes, not to the monomeric form. The trimer conformation can be found from the EM tomography data, averaging and fitting.

BLAST PDB for gp120, ~15 structures.
MAV showing sequence variations.

SAXS profile of gp120 / FAB / CD4 complex.

Physical model of gp120 trimers in 5 parts with bound CD4 and FAB
connected by magnets.

Cytoscape showing clustered HIV sequences clustered into clades
with associated PDB structures.

Glycosylation of gp120 (>50% of mass) illustrate glycans
with filled rings.

Inertia ellipsoids to show FAB orientations on gp120.

Fetch by id download caching.

Only one gp120 (SIV) has glycans.  Might demonstrating adding
them to naked gp120?