Role of N-glycans and SDF-1alpha on the coassociation of CD4 with CXCR4 at the plasma membrane of monocytic cells and blood lymphocytes.
CXCR4 is a coreceptor, along with CD4, for human immunodeficiency virus type 1 (HIV-1). Trimolecular complexes between HIV-1 glycoprotein (gp)120, CD4 and CXCR4 constitute a prerequisite for HIV entry. We studied whether CD4 is associated with CXCR4 on CD4+ CXCR4+ cells. Using the conformation-dependent anti-CXCR4 mAb 12G5, CD4 was coimmunoprecipitated with CXCR4 from the membrane of U937 cells which support HIV-1(LAI) efficient infection, and from that of peripheral blood lymphocytes (PBL). CD4 association with CXCR4 increased upon PBL coculture for 5 days with autologous monocytes, decreased upon treatment of the cells or the CD4-CXCR4 complex with either N-glycanase or stromal cell derived factor-1alpha (SDF-1alpha) and was abolished by incubation of the cells with both, N-glycanase and SDF-1alpha. This indicates that glycans are partly involved in CD4 association with CXCR4 and may partly explain the inhibitory effect of SDF-1alpha on HIV infection.
Mbemba
Elisabeth
E
Laboratoire de Biologie Cellulaire, EA 3510, Biothérapies, Bénéfices et Risques, Unité de Formation et de Recherche-Santé Médecine et Biologie Humaine, Université Paris XIII, 74 rue Marcel Cachin, 93017 Bobigny, France.
Saffar
Line
L
Gattegno
Liliane
L
D000581:Amidohydrolases / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D018920:Coculture Techniques; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D046911:Macromolecular Substances; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D011134:Polysaccharides / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020298:U937 Cells
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D046911:Macromolecular Substances; D011134:Polysaccharides; D019718:Receptors, CXCR4; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase