HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection

Simon Swingler, Beda Brichacek, Jean Marc Jacque, Catherine Ulich, Jin Zhou, Mario Stevenson

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


All primate lentiviruses (HIV-1, HIV-2, SIV) encode Nef proteins, which are important for viral replication and pathogenicity in vivo. It is not known how Nef regulates these processes. It has been suggested that Nef protects infected cells from apoptosis and recognition by cytotoxic T lymphocytes. Other studies suggest that Nef influences the activation state of the infected cell, thereby enhancing the ability of that cell to support viral replication. Here we show that macrophages that express Nef or are stimulated through the CD40 receptor release a paracrine factor that renders T lymphocytes permissive to HIV-1 infection. This activity requires the upregulation of B-cell receptors involved in the alternative pathway of T-lymphocyte stimulation. T lymphocytes stimulated through this pathway become susceptible to viral infection without progressing through the cell cycle. We identify two proteins, soluble CD23 and soluble ICAM, that are induced from macrophages by Nef and CD40L, and which mediate their effects on lymphocyte permissivity. Our results reveal a mechanism by which Nef expands the cellular reservoir of HIV-1 by permitting the infection of resting T lymphocytes.

Original languageEnglish (US)
Pages (from-to)213-219
Number of pages7
Issue number6945
StatePublished - Jul 10 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


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