John A.G. Briggs

Retrovirus structure and assembly

The structural genomics of HIV

Gag

Immature virion

Immature HIV

Gag cleavage – can be inhibited

p2 p1p17 p24 p7

maturation

MMTV

HIV

2 pathways of Retrovirus formation.

Immature virion

Immature virion

Internal scaffold domainCytoplasmic retention motif

MMTV

HIV

Envelopment?

Immature virion

cytosol

cytosol

maturation

Finch/Sundquist lab

Core formed from ~1200 capsid proteins

Arranged in ~96Å hexagonal lattice

maturation

What is the structure of the lattice here?

In-vitro assembledImmature HIV-1

If it is made from 80A hexagons, with six proteins per hexagon then 3400 ± 200 gag proteins

Mean mass: 165 ± 29 MDa

3800 ± 700 gag proteins

Scanning Transmission Electron Microscopy

145nm immature virion formed from ~5000 Gag proteins

Arranged in ~80 Å hexagonal lattice

Immature virion

Tighter hexagonal lattice with 8 nm unit cell.

~5000 gag proteins form a complete shell for a 145 nm virus

Mature virion

Looser hexagonal lattice with 9.6 nm unit cell.

~1200 CA proteins form the conical core, leaving a large number elsewhere

VirologyUniversity of HeidelbergUniversity of OxfordCornell University

Hans-Georg KraüsslichBarbara MüllerMarko LampeBärbel GlassMarc JohnsonVolker VogtQuentin Sattentau

Electron MicroscopyUniversity of OxfordMax-Planck Institute for Biochemistry

Stephen FullerKay GrünewaldFriedrich FörsterThomas WilkGiulia Zanetti