Kinetics of HIV-1 capsid uncoating revealed by single-molecule analysis.
Elife
; 72018 06 07.
Article
em En
| MEDLINE
| ID: mdl-29877795
ABSTRACT
Uncoating of the metastable HIV-1 capsid is a tightly regulated disassembly process required for release of the viral cDNA prior to nuclear import. To understand the intrinsic capsid disassembly pathway and how it can be modulated, we have developed a single-particle fluorescence microscopy method to follow the real-time uncoating kinetics of authentic HIV capsids in vitro immediately after permeabilizing the viral membrane. Opening of the first defect in the lattice is the rate-limiting step of uncoating, which is followed by rapid, catastrophic collapse. The capsid-binding inhibitor PF74 accelerates capsid opening but stabilizes the remaining lattice. In contrast, binding of a polyanion to a conserved arginine cluster in the lattice strongly delays initiation of uncoating but does not prevent subsequent lattice disassembly. Our observations suggest that different stages of uncoating can be controlled independently with the interplay between different capsid-binding regulators likely to determine the overall uncoating kinetics.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírion
/
Capsídeo
/
HIV-1
/
Proteínas do Capsídeo
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Austrália