OX40 stimulation by gp34/OX40 ligand enhances productive human immunodeficiency virus type 1 infection.

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.

• 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)

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

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