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-α. The presence of TNF-α is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-α 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 261-270 |
| Number of pages | 10 |
| Journal | Virology |
| Volume | 314 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 15 2003 |
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Keywords
- CD40
- HIV-1 latency
- Macrophages
- Reactivation
ASJC Scopus subject areas
- Virology
- Infectious Diseases
Cite this
CD154-CD40-induced reactivation of latent HIV-1 infection. / Kutsch, Olaf; Levy, David; Kosloff, Barry R.; Shaw, George M.; Benveniste, Etty N.
In: Virology, Vol. 314, No. 1, 15.09.2003, p. 261-270.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD154-CD40-induced reactivation of latent HIV-1 infection
AU - Kutsch, Olaf
AU - Levy, David
AU - Kosloff, Barry R.
AU - Shaw, George M.
AU - Benveniste, Etty N.
PY - 2003/9/15
Y1 - 2003/9/15
N2 - 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-α. The presence of TNF-α is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-α 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.
AB - 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-α. The presence of TNF-α is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-α 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.
KW - CD40
KW - HIV-1 latency
KW - Macrophages
KW - Reactivation
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U2 - 10.1016/S0042-6822(03)00413-6
DO - 10.1016/S0042-6822(03)00413-6
M3 - Article
VL - 314
SP - 261
EP - 270
JO - Virology
JF - Virology
SN - 0042-6822
IS - 1
ER -