CD154-CD40-induced reactivation of latent HIV-1 infection.
Virology
; 314(1): 261-70, 2003 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-14517079
ABSTRACT
Reservoirs of latent HIV-1 in T cells and macrophages pose one of the major obstacles that hamper final eradication of HIV-1 from infected patients. Targeting costimulatory molecules expressed on cell types harboring latent HIV-1 to achieve reactivation may provide a new approach to overcome this problem. One such molecule is CD40, a member of the tumor necrosis factor (TNF)-receptor family. Using THP89GFP cells as a model for latently infected macrophages, we demonstrate that trimeric forms of recombinant CD154 allow for the direct reactivation of latent HIV-1 infection. Reactivation is augmented by the release of TNF-alpha. The presence of TNF-alpha is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-alpha are sufficiently high to reactivate latent HIV-1 in a latently HIV-1-infected T-cell line (J89GFP). Taken together, our results demonstrate that costimulatory molecules may be attractive targets to reactivate latent HIV-1 in infected patients.
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Base de dados:
MEDLINE
Assunto principal:
Ativação Viral
/
HIV-1
/
Latência Viral
/
Antígenos CD40
/
Ligante de CD40
/
Macrófagos
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article