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 journalArticle

194 Citations (Scopus)

Abstract

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
Pages (from-to)213-219
Number of pages7
JournalNature
Volume424
Issue number6945
DOIs
StatePublished - Jul 10 2003
Externally publishedYes

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CD40 Ligand
HIV-1
Macrophages
T-Lymphocytes
Infection
Primate Lentiviruses
nef Gene Products
HIV-2
Cytotoxic T-Lymphocytes
Virus Diseases
Lymphocyte Activation
HIV Infections
Virulence
Cell Cycle
B-Lymphocytes
Up-Regulation
Lymphocytes
Apoptosis
Proteins

ASJC Scopus subject areas

  • General

Cite this

HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. / Swingler, Simon; Brichacek, Beda; Jacque, Jean Marc; Ulich, Catherine; Zhou, Jin; Stevenson, Mario.

In: Nature, Vol. 424, No. 6945, 10.07.2003, p. 213-219.

Research output: Contribution to journalArticle

Swingler, S, Brichacek, B, Jacque, JM, Ulich, C, Zhou, J & Stevenson, M 2003, 'HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection', Nature, vol. 424, no. 6945, pp. 213-219. https://doi.org/10.1038/nature01749
Swingler, Simon ; Brichacek, Beda ; Jacque, Jean Marc ; Ulich, Catherine ; Zhou, Jin ; Stevenson, Mario. / HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. In: Nature. 2003 ; Vol. 424, No. 6945. pp. 213-219.
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