Expression and utilization of co-receptors in HIV and simian immunodeficiency virus infection of megakaryocytes

Objective: To analyse the expression and specificity of co-receptors for th e entry of HIV and simian immunodeficiency virus (SIV) into megakaryocytes. Design and methods: The expression of co-receptors was determined by flow c ytometric analysis in combination with reverse transcription-polymerase cha in (RT-PCR) reaction. The specificity of co-receptors in virus entry was de termined by the infection of HIV-1 pseudotyped with X4- (HXB2), R5- (YU2), or R5X4-tropic (89.6) envelope proteins of HIV-I or with envelope proteins of SIVpbj1.9. Results: The model human erythroleukemia (HEL) cell line, exhibiting megaka ryocytic-like properties, expressed CCR5, CCR3, CXCR4, and CPR15/BOB, and a ll viruses except YU2 (R5) efficiently entered the cells. The blocking of v irus entry with specific chemokines showed that the entry of HXB2 (X4) was impaired by SDF-1 beta but not by other chemokines, indicating that CXCR4 w as a major coreceptor for the entry of HXB2. Primary human bone marrow mega karyocytes displayed a different repertoire of co-receptor expression from that of HEL cells, as all viruses except YU2 efficiently entered these cell s. However, chemokine blocking experiments showed that the entry of HXB2 in to primary bone marrow megakaryocytes was insufficiently blocked by SDF-1 b eta compared with the entry into HEL cells, suggesting that alternative co- receptors could be employed for the entry of X4 virus into bone marrow cell s. Conclusion: These data suggest that cells of megakaryocytic lineage are sus ceptible to infection by X4 viruses, with less marked susceptibility to R5 isolates, and that SDF-1 beta efficiently blocks the infection of HEL cells but not of primary bone marrow megakaryocytes. Our data reveal that novel co-receptors are probably utilized for the entry of X4 virus into megakaryo cytes. (C) 1999 Lippincott Williams & Wilkins.