HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection
| Autor: | Simon Swingler, Beda Brichacek, Catherine Ulich, Mario Stevenson, Jean Marc Jacque, Jin Zhou |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
T-Lymphocytes viruses CD40 Ligand CD2 Antigens Cell Communication Lymphocyte Activation Virus Replication Article Gene Products nef Paracrine signalling Virus latency medicine Humans Cytotoxic T cell Macrophage nef Gene Products Human Immunodeficiency Virus CD40 Antigens Cells Cultured B-Lymphocytes Multidisciplinary CD40 biology Receptors IgE Macrophages virus diseases T lymphocyte Intercellular Adhesion Molecule-1 medicine.disease Virology Virus Latency Viral replication HIV-1 biology.protein Leukocyte Common Antigens Signal transduction Signal Transduction |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature01749 |
| Popis: | All primate lentiviruses (HIV-1, HIV-2, SIV) encode Nef proteins, which are important for viral replication and pathogenicity in vivo(1-3). 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(4-6). Other studies suggest that Nef influences the activation state of the infected cell, thereby enhancing the ability of that cell to support viral replication(7-10). 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|