Inhibition of CXCR4-tropic HIV-1 infection by lipopolysaccharide: evidence of different mechanisms in macrophages and T lymphocytes.
Bacterial LPS protects primary human macrophages from infection by CCR5-tropic HIV-1 isolates through the release of the CC chemokines RANTES and macrophage inflammatory protein-1 alpha and -1 beta. Here, we show that LPS also suppresses infection of macrophages by CXCR4-tropic HIV-1 isolates. A marked down-regulation of both CD4 and CXCR4 expression was associated with this effect. Furthermore, a soluble factor(s) released by macrophages upon LPS treatment inhibited infection with CXCR4-tropic HIV-1 isolate viruses in both macrophages and T lymphocytes. Infection of both cell types appeared to be blocked at the level of viral entry and was independent of stromal cell-derived factor-1, the only known natural ligand of CXCR4. Moreover, the suppressive effect of LPS was unrelated to the release of IFN-alpha and -beta, macrophage-derived chemokine, leukemia inhibitory factor, or TNF-alpha. These results suggest the existence of potent HIV-1 inhibitory factor(s), uncharacterized to date, released by activated cells of the mononuclear phagocytic system.
Verani
Alessia
A
Human Virology Unit, DIBIT, San Raffaele Scientific Institute, Milan, Italy. alessia.verani@hsr.it
Sironi
Francesca
F
Siccardi
Antonio G
AG
Lusso
Paolo
P
Vercelli
Donata
D
D019380:Anti-HIV Agents / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018832:Molecular Chaperones / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011506:Proteins; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D012995:Solubility; D013491:Suppressor Factors, Immunologic / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019380:Anti-HIV Agents; C515482:CCL22 protein, human; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; D054422:Chemokine CCL22; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D007106:Immune Sera; D016898:Interferon-alpha; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; D011506:Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha