CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection.
Granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced monocyte-derived macrophages (GM-MPhi) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MPhi) produce a large amount of HIV-1. M-MPhi express a high level of Hck and a large isoform of C/EBPbeta, and HIV-1 infection increases the expression of Hck but not of C/EBPbeta. GM-MPhi express a high level of C/EBPbeta and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPbeta but decreases that of Hck. Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication. Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.
Komuro
Iwao
I
Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.
Yokota
Yasuko
Y
Yasuda
Sachiko
S
Iwamoto
Aikichi
A
Kagawa
Kiyoko S
KS
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D009000:Monocytes / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck; D014779:Virus Replication
D022782:CCAAT-Enhancer-Binding Protein-beta; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck