Discrete partitioning of HIV-1 Env forms revealed by viral capture.
Retrovirology
; 12: 81, 2015 Sep 24.
Article
en En
| MEDLINE
| ID: mdl-26399966
ABSTRACT
BACKGROUND:
The structure of HIV-1 envelope glycoprotein (Env) is flexible and heterogeneous on whole virions. Although functional Env complexes are thought to require trimerization of cleaved gp41/gp120 heterodimers, variable processing can result in the potential incorporation of non-functional uncleaved proteins (gp160), non-trimeric arrangements of gp41/gp120 heterodimers, and gp120 depleted gp41 stumps. The potential distribution of functional and non-functional Env forms across replication-competent viral populations may have important implications for neutralizing and non-neutralizing antibody functions. This study applied an immuno-bead viral capture assay (VCA) to interrogate the potential distribution (heterologous vs homologous) of functional and non-functional forms of virion associated Env.RESULTS:
The VCA revealed a significant association between depletion of infectious virions and virion Env incorporation, but not between infectivity and p24-gag. Three distinct subpopulations of virions were identified within pools of genetically homogenous viral particles. Critically, a significant subpopulation of infectious virions were exclusively captured by neutralizing antibodies (nAbs) indicative of a homologous distribution of functional trimeric Env forms. A second infectious subpopulation bound both neutralizing and non-neutralizing antibodies (nnAbs) representative of a heterologous distribution of Env forms, while a third non-infectious subpopulation was predominantly bound by nnAbs recognizing gp41 stumps.CONCLUSIONS:
The observation that a distinct and significant subpopulation of infectious virions is exclusively captured by neutralizing antibodies has important implications for understanding antibody binding and neutralization, as well as other antibody effector functions.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Virión
/
Proteína gp120 de Envoltorio del VIH
/
VIH-1
/
Proteínas gp160 de Envoltorio del VIH
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Retrovirology
Asunto de la revista:
VIROLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos