Journal of Virology, August 2001, p. 6748-6757, Vol. 75, No. 15
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.15.6748-6757.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Departments of Microbiology and Molecular Virology, School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519,1 Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of The Ryukyus, Okinawa 903-0215,2 Department of Virology, Tohoku University School of Medicine, Sendai 980-8575,3 and Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo 113-8510,4 Japan
Received 2 November 2000/Accepted 20 April 2001
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-
) and TNF-
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
B site of the HIV-1 long terminal repeat,
and the OX40-gp34 interaction activated NF-
B consisting of p50 and
p65 subunits. When primary activated CD4+ T cells acutely
infected with HIV-1NL4-3 (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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