TY - JOUR
T1 - Signaling through the lymphotoxin-β receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-α
AU - Marshall, William L.
AU - Brinkman, Brigitta M N
AU - Ambrose, Christine M.
AU - Pesavento, Patricia
AU - Uglialoro, Adele M.
AU - Teng, Edna
AU - Finberg, Robert W.
AU - Browning, Jeffrey L.
AU - Goldfeld, Anne E.
PY - 1999/5/15
Y1 - 1999/5/15
N2 - The level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis. Among host immune factors, the cytokine TNF-α has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems. Here, we demonstrate that signaling through the TNF receptor family member, the lymphotoxin-β (LT-β) receptor (LT-βR), also regulates HIV-1 replication. Furthermore, HIV-1 replication is cooperatively stimulated when the distinct LT-βR and TNF receptor systems are simultaneously engaged by their specific ligands. Moreover, in a physiological coculture cellular assay system, we show that membrane-bound TNF-α ancd LT-α1β2 act virtually identically to their soluble forms in the regulation of HIV-1 replication. Thus, cosignaling via the LT-β and TNF- α receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes. Intriguingly, surface expression of LT-α1β2 is up-regulated on a T cell line acutely infected with HIV-1, suggesting a positive feedback loop between HIV-1 infection, LT-α1β2 expression, and HIV-1 replication. Given the critical role that LT-α1β2 plays in lymphoid architecture, we speculate that LT-α1β2 may be involved in HIV-associated abnormalities of the lymphoid organs.
AB - The level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis. Among host immune factors, the cytokine TNF-α has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems. Here, we demonstrate that signaling through the TNF receptor family member, the lymphotoxin-β (LT-β) receptor (LT-βR), also regulates HIV-1 replication. Furthermore, HIV-1 replication is cooperatively stimulated when the distinct LT-βR and TNF receptor systems are simultaneously engaged by their specific ligands. Moreover, in a physiological coculture cellular assay system, we show that membrane-bound TNF-α ancd LT-α1β2 act virtually identically to their soluble forms in the regulation of HIV-1 replication. Thus, cosignaling via the LT-β and TNF- α receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes. Intriguingly, surface expression of LT-α1β2 is up-regulated on a T cell line acutely infected with HIV-1, suggesting a positive feedback loop between HIV-1 infection, LT-α1β2 expression, and HIV-1 replication. Given the critical role that LT-α1β2 plays in lymphoid architecture, we speculate that LT-α1β2 may be involved in HIV-associated abnormalities of the lymphoid organs.
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M3 - Article
C2 - 10229841
AN - SCOPUS:0033562999
VL - 162
SP - 6016
EP - 6023
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -