Infection of monocytic cells by HIV1: combined role of FcR and CD4.
Human immunodeficiency virus (HIV) complexed with human anti-HIV IgG can attach to Fc gamma receptors (Fch) of mononuclear phagocytes. To determine whether the FcR-mediated infection that results also requires interaction between HIV gp120 and cell membrane CD4, monocytic cells of the U937 line were transiently treated with phorbol 12,13-dibutyrate (PDB) so that they temporarily presented a CD4-FcR+ phenotype at the time of HIV infection. HIV production was not abolished, but only significantly delayed after infection of these cells with free virus. Leu3a monoclonal antibody or soluble recombinant CD4 completely blocked this delayed infection. This indicates that enough CD4 still remained at the membrane to allow infection of a reduced cell number. Infection of PDB-treated cells with virus preincubated with high anti-HIV IgG concentrations was inhibited, contrasting with what was observed with control cells infected under the same conditions. Inhibition of infection was also observed when HIV became attached to untreated U937 cells through the binding of CD4-IgG hybrid molecules to FcR. Thus, the binding of IgG-coated virus to FcR is not sufficient in itself to elicit productive infection of monocytic cells, which still requires the interaction of viral gp120 and membrane CD4.
Jouault
T
T
Laboratoire de Biologie et Génétique des Déficits Immunitaires, CERVI, Groupe Hospitalier Pitié-Salpétrière, Paris, France.
Chapuis
F
F
Bahraoui
E
E
Gluckman
J C
JC
D000943:Antigens, Differentiation / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014779:Virus Replication
D000943:Antigens, Differentiation; D015704:CD4 Antigens; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D015240:Phorbol 12,13-Dibutyrate