John A.G. Briggs Retrovirus structure and assembly

The structural genomics of HIV

Gag

Immature virion

Immature HIV

Gag cleavage – can be inhibited p2p1 p17p24p7

maturation

MMTV HIV 2 pathways of Retrovirus formation. Immature virion

Internal scaffold domain Cytoplasmic retention motif

MMTV HIV Envelopment? Immature virion

cytosol

maturation

Finch/Sundquist lab

Core formed from ~1200 capsid proteins Arranged in ~96 Å 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

Virology University of Heidelberg University of Oxford Cornell University Hans-Georg Kraüsslich Barbara Müller Marko Lampe Bärbel Glass Marc Johnson Volker Vogt Quentin Sattentau Electron Microscopy University of Oxford Max-Planck Institute for Biochemistry Stephen Fuller Kay Grünewald Friedrich Förster Thomas Wilk Giulia Zanetti