Selective up-regulation of functional CXCR4 expression in erythroid cells by HIV-1 Tat protein.
CXCR4 is the high affinity receptor for the SDF-1 alpha chemokine and represents the main coreceptor for HIV-1 T-tropic strains. The surface expression of CXCR4 was analysed in CD34+ haematopoietic progenitors, induced to differentiate along the erythroid or granulocytic lineages, in liquid cultures supplemented or not with HIV-1 Tat protein. At concentrations as low as 1-10 ng/ml, synthetic Tat protein significantly increased the surface expression of CXCR4 in erythroid but not in granulocytic cells. The Tat-mediated up-regulation of surface CXCR4 was accompanied by a concomitant increase of CXCR4 mRNA and total CXCR4 protein content in cells developing along the erythroid lineage after 6-10 days of culture. Moreover, addition of SDF-1 alpha (200 ng/ml) induced a significant higher rate of apoptosis in Tat-treated erythroid cells in comparison with control cells. These results demonstrated for the first time a direct positive role in haematopoietic gene regulation of Tat protein, and suggest the possible involvement of Tat in HIV-1-induced anaemia.
Gibellini
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Department of Clinical and Experimental Medicine, Microbiology Section, University of Bologna, Bologna, Italy. rabbiloew@libero.it
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Vitone
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Rizzo
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Maldini
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La Placa
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Zauli
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D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015696:Gene Products, tat; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D054322:tat Gene Products, Human Immunodeficiency Virus