Differentiation of promonocytic U937 subclones into macrophagelike phenotypes regulates a cellular factor(s) which modulates fusion/entry of macrophagetropic human immunodeficiency virus type 1.
Monocytes/macrophages (M/M) and CD4+ T cells are two important targets of human immunodeficiency virus (HIV) infection. Different strains of HIV-1 vary markedly in their abilities to infect cells belonging to the M/M lineage. Macrophagetropic (M-tropic) HIV-1 strains replicate well in primary lymphocytes as well as in primary macrophages; however, they generally infect T-cell lines poorly, if at all. Although promonocytic cell lines such as U937 have been used as in vitro models of HIV-1 infection of M/M, these cell lines are susceptible to certain T-cell-tropic (T-tropic) HIV-1 strains but are resistant to M-tropic HIV-1. In this study, we demonstrate that (i) certain U937 clones ("plus" clones), which are susceptible only to T-tropic HIV-1, become highly susceptible to M-tropic HIV-1 upon differentiation with retinoic acid (RA); (ii) other U937 clones ("minus" clones), which are resistant to both T- and M-tropic HIV-1, remain resistant to both viruses; and (iii) RA treatment induces expression of CCR5, a fusion/entry cofactor for M-tropic HIV-1 in both types of U937 clones, and yet enhances the fusogenicity of the plus clones, but not the minus clones, with M-tropic Env's. These results indicate that the major restriction of M-tropic HIV-1 infection in promonocytic cells occurs at the fusion/entry level, that differentiation into macrophage-like phenotypes renders some of these cells highly susceptible to infection with M-tropic HIV-1, and that CD4 and CCR5 may not be the only determinants of fusion/entry of M-tropic HIV-1 in these cells.
Moriuchi
H
H
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. hmoriuchi@atlas.niaid.nih.gov
Moriuchi
M
M
Fauci
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AS
D002454:Cell Differentiation; D015686:Gene Products, env / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D008561:Membrane Fusion; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D010641:Phenotype; D019713:Receptors, CCR5 / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015686:Gene Products, env; D008024:Ligands; D019713:Receptors, CCR5; D014212:Tretinoin