Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV

AIDS. 2003 Jan 3;17(1):33-42. doi: 10.1097/00002030-200301030-00006.

Abstract

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.

Design: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blood Platelets / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / pathogenicity*
  • Humans
  • Megakaryocytes / metabolism*
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Polymerase Chain Reaction / methods
  • Receptors, CXCR4 / metabolism*

Substances

  • Platelet Membrane Glycoprotein IIb
  • Receptors, CXCR4