Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV.
OBJECTIVE
Under some circumstances the HIV virus may infect cells that do not express receptors essential to HIV-entry. We hypothesized that platelet- and megakaryocyte-derived microparticles (MP) could play a role in such infections. MP are circular membrane fragments shed from the surface of eukaryotic cells. After adhesion to target cells, MP may transfer membrane-associated proteins to these cells. We found that peripheral blood platelet- (PMP) and megakaryocyte-derived MP (MegaMP) that highly express CXCR4 may transfer this receptor from the surface of platelets or megakaryocytes to the surface of CXCR4-null cells.


METHODS
Since this mechanism could potentially allow CD4+/CXCR4-null cells to become infected by T-tropic HIV, we incubated several human CD4+/CXCR4-null cells such as normal erythroblasts, glioblastomas U87, MAGI and hematopoietic cell lines UT-7, HEL and TF-1 with PMP or MegaMP. We found that these cells became CXCR4+. We next exposed these cells to X4-HIV (IIIB) and evaluated their susceptibility to infection by PCR, ELISA, and morphological analysis.


RESULTS
We observed in all instances that after CD4+/CXCR4-null cell lines 'acquired' CXCR4 from PMP or MegaMP, they could became infected by X4 HIV.


CONCLUSIONS
We postulate that both PMP and MegaMP may play a novel and important role in spreading HIV-1 infection by transferring the CXCR4 co-receptor to CD4+/CXCR4-null cells.
Rozmyslowicz
Tomasz
T
Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
Majka
Marcin
M
Kijowski
Jacek
J
Murphy
Samuel L
SL
Conover
Dareus O
DO
Poncz
Mortimer
M
Ratajczak
Janina
J
Gaulton
Glen N
GN
Ratajczak
Mariusz Z
MZ
D001792:Blood Platelets / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism*; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D019718:Receptors, CXCR4 / Q000378:metabolism*
D040201:Platelet Membrane Glycoprotein IIb; D019718:Receptors, CXCR4