Abstract |
OX40 is a member of the tumor necrosis factor ( TNF) receptor superfamily and known to be an important costimulatory molecule expressed on activated T cells. To investigate the role of costimulation of OX40 in human immunodeficiency virus type 1 (HIV-1) infection by its natural ligand, gp34, the OX40-transfected ACH-2 cell line, ACH-2/OX40, chronically infected with HIV-1, was cocultured with paraformaldehyde (PFA)-fixed gp34-transfected mouse cell line, SV-T2/gp34. The results showed that HIV-1 production was strongly induced. This was followed by apparent apoptosis, and both processes were specifically inhibited by the gp34-specific neutralizing monoclonal antibody 5A8. Endogenous TNF alpha ( TNF-alpha) and TNF-beta production were not involved in the enhanced HIV-1 production. Furthermore, enhanced HIV-1 transcription in gp34-stimulated ACH-2/OX40 cells was dependent on the kappa B site of the HIV-1 long terminal repeat, and the OX40-gp34 interaction activated NF-kappa B consisting of p50 and p65 subunits. When primary activated CD4(+) T cells acutely infected with HIV-1(NL4-3) (CXCR4-using T-cell-line-tropic) were cocultured with PFA-fixed gp34(+) human T-cell leukemia virus type 1-bearing MT-2 cells or SV-T2/gp34 cells, HIV-1 production was also markedly enhanced. The enhancement was again significantly inhibited by 5A8. The present study first shows that OX40-gp34 interaction stimulates HIV-1 expression and suggests that OX40 triggering by gp34 may play an important role in enhancing HIV-1 production in both acutely and latently infected CD4(+) T cells in vivo.
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Authors | Y Takahashi, Y Tanaka, A Yamashita, Y Koyanagi, M Nakamura, N Yamamoto |
Journal | Journal of virology
(J Virol)
Vol. 75
Issue 15
Pg. 6748-57
(Aug 2001)
ISSN: 0022-538X [Print] United States |
PMID | 11435553
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lymphotoxin-alpha
- Membrane Glycoproteins
- NF-kappa B
- OX40 Ligand
- Receptors, OX40
- Receptors, Tumor Necrosis Factor
- Recombinant Fusion Proteins
- TNFRSF4 protein, human
- TNFSF4 protein, human
- Tnfrsf4 protein, mouse
- Tnfsf4 protein, mouse
- Tumor Necrosis Factor Receptor Superfamily, Member 7
- Tumor Necrosis Factor-alpha
- Tumor Necrosis Factors
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Topics |
- Animals
- Apoptosis
- Binding Sites
- CD4-Positive T-Lymphocytes
(cytology, metabolism, virology)
- Cell Line
- Cells, Cultured
- Gene Expression Regulation, Viral
- HIV Long Terminal Repeat
- HIV-1
(metabolism, physiology)
- Human T-lymphotropic virus 1
- Humans
- Lymphotoxin-alpha
(metabolism)
- Membrane Glycoproteins
(genetics, metabolism)
- Mice
- Mice, Inbred BALB C
- NF-kappa B
(metabolism)
- OX40 Ligand
- Receptors, OX40
- Receptors, Tumor Necrosis Factor
- Recombinant Fusion Proteins
(genetics, metabolism)
- Transcription, Genetic
- Tumor Necrosis Factor Receptor Superfamily, Member 7
(genetics, metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
- Tumor Necrosis Factors
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