Signaling through the lymphotoxin-β receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-α

William L. Marshall, Brigitta M N Brinkman, Christine M. Ambrose, Patricia Pesavento, Adele M. Uglialoro, Edna Teng, Robert W. Finberg, Jeffrey L. Browning, Anne E. Goldfeld

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6016-6023
Number of pages8
JournalJournal of Immunology
Volume162
Issue number10
StatePublished - May 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Marshall, W. L., Brinkman, B. M. N., Ambrose, C. M., Pesavento, P., Uglialoro, A. M., Teng, E., Finberg, R. W., Browning, J. L., & Goldfeld, A. E. (1999). Signaling through the lymphotoxin-β receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-α. Journal of Immunology, 162(10), 6016-6023.