Transmembrane domain membrane proximal external region but not surface unit-directed broadly neutralizing HIV-1 antibodies can restrict dendritic cell-mediated HIV-1 trans-infection.
J Infect Dis
; 205(8): 1248-57, 2012 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-22396600
ABSTRACT
BACKGROUND:
Although broadly neutralizing antibodies (bNAbs) have been shown to block a diverse array of cell-free human immunodeficiency type 1 (HIV-1) infections, it remains unclear whether these antibodies exhibit similar potency against mature dendritic cell (mDC)-mediated HIV-1 trans-infection.METHODS:
Sensitivity to bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16, b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both cell-free and mDC-mediated infections of TZM-bl and CD4(+) T cells.RESULTS:
Compared with cell-free infection, mDC-mediated infection was significantly less susceptible to gp120-directed bNAbs for the majority of virus isolates. A b12 antigen-binding fragment blocked both cell-free and mDC-mediated infection with equal efficiency. In contrast, cell-free and mDC-associated viruses were equally sensitive to gp41-directed bNAbs. Anti-gp41 bNAbs bound to the surface of mDCs and localized at the mDC-T cell synaptic junctions in the absence of virus.CONCLUSIONS:
Anti-gp41 bNAbs have the potential to inhibit mDC-mediated HIV-1 infection because they bind plasma membranes prior to the formation of an infectious synapse, positioning them to neutralize subsequent virus transfer. As opposed to gp120-directed antibodies, anti-gp41 bNAbs might prevent HIV-1 infection if transmission or spread at the initial site of invasion occurs from a DC-associated source.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Anti-HIV
/
Infecções por HIV
/
HIV-1
/
Anticorpos Neutralizantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article